Basic extraction of psychoactive compounds from psychoactive organisms

ABSTRACT

This invention relates to the extraction of psychoactive compounds from organisms for use in medicine. Extraction is carried out with a strong acid or strong base to either promote or inhibit dephosphorylation. The extract in the slurry form is standardized with added excipient so that when it is dried the powdered composition has a specified total psychoactive alkaloid concentration, with a known ratio of phosphorylated to dephosphorylated psychoactive alkaloids.

RELATED APPLICATIONS

This application is a continuation of Ser. No. 17/348,697 filed Jun. 15,2021, which is a continuation of International Application No.PCT/CA2021/050813 filed Jun. 14, 2021, which claims priority fromCanadian Application No. 3089455 filed on Aug. 7, 2020, CanadianApplication No. 3088384 filed on Jul. 29, 2020, which claim the benefitof U.S. Provisional Patent Application No. 63/040,317 filed on Jun. 17,2020, and U.S. Provisional Patent Application No. 63/046,089 filed onJun. 30, 2020, each of which are incorporated by reference in theirentireties, International Application No. PCT/CA2021/050813 also claimspriority to Canadian Application No. 3097246 filed on Oct. 23, 2020,Canadian Application No. 3101765 filed on Dec. 4, 2020, and CanadianApplication No. 3103707 filed on Dec. 18, 2020, each of which areincorporated by reference in their entireties.

TECHNICAL FIELD

This application relates to a process of obtaining psychoactive alkaloidextracts. More specifically, the present invention relates tocontrolling dephosphorylation during extraction. Further, the presentinvention relates to psychoactive alkaloid compositions with controlleddephosphorylation.

BACKGROUND

Varieties of mushrooms have played important roles in most societies.The active ingredients in mushrooms have been found to have medicinalproperties including relief of symptoms of various diseases andconditions. The concentration of active ingredients for theseapplications may vary not only from species to species, but also frommushroom to mushroom inside a given species, subspecies, or variety. Thesame holds true even for different parts of the same mushroom ormycelium.

Various methods of extraction, which have been used to separate naturalextracts from a variety of mushrooms, have resulted in difficulties withlarge crop-to-crop variability. A large variability within a singleplant or fungus sometimes causes inconsistent concentration of theactive psychoactive compound and its stability. Different solventchoices extract the psychoactive compounds equally, some of themelectively extract one or the other, and some convert the compoundsbetween each other or degrade them into non-psychoactive compounds. Manyextraction processes for extracting standardized concentrations of thecompounds for direct medical use are usually complex. This results inexpensive extraction processes and a high cost of isolated, naturalextracts.

U.S. Pat. No. 3,183,172 to Heim et al. relates to an industrial processfor the isolation of active compounds from mushrooms grown underpredetermined conditions. With the predetermined growing conditions,mushrooms grew with ten times more active mycelium and sclerotium andincreased concentrations of psychoactive compounds. However, a largeportion of the target compounds were lost during the extraction processor not extracted at all. In addition, the solvent and solvent systemsused during the extraction process were materials such as methanol,acetone, dichloromethane, diethyl ether, or others known to be toxic tohumans, even in small quantities.

Extraction methods currently described in the art are inefficient suchthat a large portion of the target compounds were lost during theextraction process or not extracted at all. They lack analytical data asevidence. We have replicated and measured these methods to prove theyare ineffective. In addition, they describe the use of solvents whichare known to be toxic to humans, even in small quantities.

To date, the focus has largely been on synthetic preparations of thesecompounds because of the many difficulties associated with naturallyextracted preparations. It is currently infeasible and expensive toextract psilocybin from mushrooms, and even the best chemical synthesismethods require expensive and difficult-to-source starting substrates.

Accordingly, there is a need of methods to produce high efficiency,standardized preparations of the target compounds for medical use whileusing acceptable solvent systems to create a more consistent supplychain.

SUMMARY OF INVENTION

A psychoactive alkaloid composition comprising of, by weight: 0.1-99.9%of a psychoactive alkaloid extract; and one or more preservatives up to10%, a flow agent up to 2%, 0-94% of one or more carriers, or anycombination thereof. In some embodiments, the composition comprises2-99.7% of the psychoactive alkaloid extract. In some embodiments, thecomposition comprises an antioxidant up to 0.5% by weight. In someembodiments, the composition comprises a bioavailability agent up to0.5% by weight. In some embodiments, the psychoactive alkaloid extracthas a psychoactive alkaloid concentration ranging from 0.1% to 99% byweight of the extract. In some embodiments, the one or morepreservatives are selected from ascorbic acid, citric acid, lactose,vitamin A, vitamin E, retinyl palm itate, selenium, sodium citrate,sodium ascorbate, calcium ascorbate, sodium benzoate, and potassiumbenzoate. In some embodiments, the psychoactive alkaloid extract has apsychoactive alkaloid concentration ranging from 0.1% to 20% by weightof the extract. In some embodiments, the psychoactive alkaloid extractis a purified psychoactive alkaloid extract, and the purifiedpsychoactive alkaloid extract has a psychoactive alkaloid concentrationranging from 10% to 99% by weight. In some embodiments, the compositionis in a powder form. In some embodiments, the composition comprises 10%or more of the carrier. In some embodiments, the psychoactive alkaloidis psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin,aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT(5-methoxy-N.Ndimethyltryptamine), N,N-dimethyltryptamine (DMT),4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine ergine (LSA),ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acidhydroxyethylamide (LSH), elymoclavine, ergometrinine, and/orchanoclavine, or any combination selected therefrom. In someembodiments, the psychoactive alkaloid extract comprises naturallyoccurring substances selected from the group consisting of fats, sugars,carbohydrates, chitin, chitosan, minerals, waxes and proteins. In someembodiments, the naturally occurring substances are present in thepsychoactive alkaloid extract in a concentration ranging from 1%-99.9%by weight. In some embodiments, the psychoactive alkaloid extract isfrom fungi. In some embodiments, the psychoactive alkaloid extract isfrom Psilocybe cyanescens, Psilocybe cubensis, Amanita muscaria, or anyselection therefrom. In some embodiments, the psychoactive alkaloidextract is from psychoactive plants. In some embodiments, thepsychoactive alkaloid extract is from Anadenanthera colubrina. In someembodiments, the psychoactive alkaloid extract is from Anadenantheraperegrina. In some embodiments, the psychoactive alkaloid extract isfrom psychoactive animals. In some embodiments, the psychoactivealkaloid extract is from Incilius alvarius. In some embodiments, thepsychoactive alkaloid extract is from psychoactive yeasts. In someembodiments, the flow agent is selected from silicon dioxide, stearicacid, magnesium stearate, or talc. In some embodiments, the one or morecarriers are selected from starch, maltodextrin, alpha and betacyclodextrin, microcrystalline cellulose (MCC), gum arabic, xanthum gum,guar gum, mannitol, or cellulose gum. In some embodiments, themaltodextrin is tapioca maltodextrin or rice maltodextrin. In someembodiments, the starch is potato starch. In some embodiments, the flowagent is present in the composition at 0.1 to 1.2%. In some embodiments,a first preservative of the one or more preservatives is present in thecomposition at 0.1 to 3%. In some embodiments, a second preservative ofthe one or more preservatives is present in the composition at 0.1 to3%. In some embodiments, a first carrier of the one or more carriers ispresent in the composition at 10 to 20%. In some embodiments, a secondcarrier of the one or more carriers is present in the composition at 10to 20%. In some embodiments, the composition comprises: the flow agentpresent in the composition at 0.1 to 1.2%; the one or more preservativespresent in the composition at 0.1 to 2%; and the one or more carrierspresent in the composition at 10 to 20%. In some embodiments, the flowagent is silicon dioxide; the carrier comprises maltodextrin andmannitol; and the one or more preservatives comprise ascorbic acid andcitric acid. In some embodiments, the silicon dioxide is present in thecomposition at 0.1 to 1.2%. In some embodiments, the ascorbic acid ispresent in the composition at 0.1 to 2%. In some embodiments, the citricacid is present in the composition at 0.1 to 2%. In some embodiments,the maltodextrin is present in the composition at 10 to 20%. In someembodiments, the mannitol is present in the composition at 10 to 20%. Insome embodiments, the flow agent is silicon dioxide; the carriercomprises starch and mannitol; and the one or more preservativescomprise ascorbic acid and citric acid. In some embodiments, the silicondioxide is present in the composition at 0.1 to 1.2%. In someembodiments, the ascorbic acid is present in the composition at 0.1 to2%. In some embodiments, the citric acid is present in the compositionat 0.1 to 2%. In some embodiments, the starch is present in thecomposition at 10 to 20%. In some embodiments, the mannitol is presentin the composition at 10 to 20%.

A method for generating a psychoactive alkaloid extract from apsychoactive organism, the method comprising: providing a biomass of thepsychoactive organism; contacting the biomass with 10 to 100 milliliters(mL) of solvent per gram (g) of the biomass; and evaporating the solventfrom the biomass to yield the psychoactive alkaloid extract. In someembodiments, the solvent is selected from 100% methanol, analcohol:water mixture wherein the alcohol comprises 60% to 99% of thealcohol:water mixture, an alcohol:acid mixture wherein the alcoholcomprises 60% to 99% of the alcohol:acid mixture, and acidified water.

A method for generating a psychoactive alkaloid extract from apsychoactive organism, the method comprising: providing a biomass of thepsychoactive organism; contacting the biomass with a solvent, whereinthe solvent is selected from 100% methanol, an alcohol:water mixturewherein the alcohol comprises 60% to 99% of the alcohol:water mixture,an alcohol:acid mixture wherein the alcohol comprises 60% to 99% of thealcohol:acid mixture, and acidified water; and evaporating the solventfrom the biomass to yield the psychoactive alkaloid extract. In someembodiments, the solvent is present at 10 to 100 milliliters (mL) ofsolvent per gram (g) of the biomass. In some embodiments, the solvent ispresent at 10 to 60 mL of solvent per gram of the biomass. In someembodiments, the solvent is present at 40 to 60 mL of solvent per gramof the biomass. In some embodiments, the biomass of the psychoactiveorganism is dried prior to contacting with the solvent. In someembodiments, the biomass of the psychoactive organism is reduced to aparticle size of 6 millimeters (mm) to 0.03 mm prior to contacting withthe solvent. In some embodiments, the biomass of the psychoactiveorganism is reduced to a particle size of 1 mm to 0.03 mm prior tocontacting with the solvent. In some embodiments, the biomass of thepsychoactive organism is reduced to a particle size of at least 0.074 mmprior to contacting with the solvent. In some embodiments, the biomassof the psychoactive organism is contacted with the solvent at 5° C. to95° C. In some embodiments, the biomass of the psychoactive organism iscontacted with the solvent at 20° C. to 70° C. In some embodiments, thebiomass of the psychoactive organism is contacted with the solvent at25° C. In some embodiments, the biomass of the psychoactive organism iscontacted with the solvent for 1 to 720 minutes. In some embodiments,the biomass of the psychoactive organism is contacted with the solventfor 20 to 60 minutes. In some embodiments, the biomass of thepsychoactive organism is contacted with the solvent for 30 minutes. Insome embodiments, following (b), the biomass is filtered through afilter. In some embodiments, the filter comprises a 1 micron (μm) to 10μm mesh. In some embodiments, following (b), the biomass is contractedwith a second solvent. In some embodiments, the second solvent isselected from 100% methanol, an alcohol:water mixture wherein thealcohol comprises 60% to 99% of the alcohol:water mixture, analcohol:acid mixture wherein the alcohol comprises 60% to 99% of thealcohol:acid mixture, and acidified water. In some embodiments, thesecond solvent is present at 10 to 100 milliliters (mL) of solvent pergram (g) of the biomass. In some embodiments, the solvent is present at10 to 60 mL of solvent per gram of the biomass. In some embodiments, thesolvent is present at 40 to 60 mL of solvent per gram of the biomass. Insome embodiments, the alcohol of the alcohol:water mixture, thealcohol:acid mixture, or both, is a C1-C4 primary aliphatic alcohol. Insome embodiments, the C1-C4 primary aliphatic alcohol is ethanol ormethanol. In some embodiments, the acid in the alcohol:acid mixture, theacidified water, or both, is acetic acid, adipic acid, ascorbic acid,phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic,ammonium citrate monobasic, calcium citrate, calcium fumarate, calciumgluconate, calcium phosphate dibasic, calcium phosphate, hydrochloricacid, sulphuric acid monobasic, calcium phosphate tribasic, citric acid,fumaric acid, gluconic acid, magnesium fumarate, malic acid, phosphoricacid, potassium acid tartrate, potassium citrate, potassium fumarate,sodium citrate, sodium fumarate, sodium gluconate, sodium lactate,sodium potassium hexametaphosphate, sodium potassium tartrate, sodiumpotassium tripolyphosphate, sodium pyrophosphate tetrabasic, sodiumtripolyphosphate, tartaric acid, and any combination therefrom. In someembodiments, the solvent, second solvent, or both is buffered to a pH ofeither 4 or less, or 10 or greater. In some embodiments, the solvent,second solvent, or both is buffered with ammonium bicarbonate, ammoniumcarbonate, ammonium hydroxide, calcium acetate, calcium carbonate,calcium chloride, calcium hydroxide, calcium lactate, calcium oxide,calcium phosphate, dibasic, calcium phosphate monobasic, magnesiumcarbonate, potassium aluminum sulphate, potassium bicarbonate, potassiumcarbonate, potassium hydroxide, potassium lactate, potassium phosphate,dibasic, potassium pyrophosphate, tetrabasic, potassium phosphatetribasic, potassium tripolyphosphate, sodium acetate, sodium acidpyrophosphate, sodium aluminum phosphate, sodium aluminum sulphate,sodium bicarbonate, sodium bisulphate, sodium carbonate, sodiumhexametaphosphate, sodium hydroxide, sodium lactate, sodium phosphatedibasic, sodium phosphate monobasic, sodium phosphate tribasic, and anycombination therefrom. In some embodiments, the solvent, second solvent,or both is buffered with acetic acid, adipic acid, ascorbic acid,phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic,ammonium citrate monobasic, calcium citrate, calcium fumarate, calciumgluconate, calcium phosphate dibasic, calcium phosphate, hydrochloricacid, sulphuric acid monobasic, calcium phosphate tribasic, citric acid,fumaric acid, gluconic acid, magnesium fumarate, malic acid, phosphoricacid, potassium acid tartrate, potassium citrate, potassium fumarate,sodium citrate, sodium fumarate, sodium gluconate, sodium lactate,sodium potassium hexametaphosphate, sodium potassium tartrate, sodiumpotassium tripolyphosphate, sodium pyrophosphate tetrabasic, sodiumtripolyphosphate, tartaric acid, and any combination therefrom. In someembodiments, the psychoactive alkaloid is psilocybin, psilocin,baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin,bufotenidine, 5-MeO-DMT (5-methoxy-N.Ndimethyltryptamine),N,N-dimethyltryptamine (DMT), 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine ergine (LSA), ergonovine,ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide(LSH), elymoclavine, ergometrinine, and/or chanoclavine, or anycombination selected therefrom. In some embodiments, the solvent has apH of 10 or greater and the psychoactive alkaloid extract comprisesgreater than 50% of the phosphorylated psychoactive alkaloid. In someembodiments, the psychoactive alkaloid extract comprises greater than90% of a phosphorylated psychoactive alkaloid. In some embodiments, thephosphorylated alkaloid is psilocybin, baeocystin, norbaeocystin,aeruginascin, or any combination therefrom. In some embodiments, thesolvent has a pH of 4 or less and the psychoactive alkaloid extractcomprises greater than 50% of a dephosphorylated psychoactive alkaloid.In some embodiments, the psychoactive alkaloid extract comprises greaterthan 90% of the dephosphorylated psychoactive alkaloid. In someembodiments, the dephosphorylated alkaloid is psilocin, norpsilocin,4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine, or anycombination therefrom. In some embodiments, the psychoactive organism isa plant, animal, fungus, protist, or bacterium. In some embodiments, thepsychoactive organism is Psilocybe cyanescens, Psilocybe cubensis,Amanita muscaria, or any selection therefrom. In some embodiments, thepsychoactive organism is Anadenanthera colubrina or Anadenantheraperegrina. In some embodiments, the psychoactive organism is Inciliusalvarius. In some embodiments, the psychoactive organism is yeast.

A process for forming an extract of psychoactive alkaloids frompsychoactive organisms comprising the steps of: soaking a biomass ofdried, raw psychedelic fungus in a solvent selected from the groupconsisting of ethanol, a water-ethanol mixture, methanol, and awater-methanol mixture in order to dissolve the psychoactive alkaloidsin the solvent; filtering an undissolved portion of the biomass from thesolvent; evaporating the solvent sufficiently to remove the solventcompletely, leaving a concentrated slurry or a residue that is convertedto the concentrated slurry by adding water thereto: and standardizingthe concentrated slurry by adding thereto a quantity of carrier measuredto achieve a specified purity of extract. In some embodiments, thestandardizing comprises: measuring a psychoactive alkaloid content inthe concentrated slurry; and using the psychoactive alkaloid content,the specified purity and a volume of the concentrated slurry todetermine the quantity of carrier. In some embodiments, the processcomprises drying the concentrated slurry to result in the extract,wherein the extract is a powdered extract. In some embodiments, thesolvent is a water-ethanol or water-methanol alkaline buffered solution.In some embodiments, the solvent has a pH of 11-12. In some embodiments,the solvent is buffered with sodium hydroxide, the process comprising,between the filtering and evaporating steps, adjusting the solvent to apH of 4-9 using phosphoric acid. In some embodiments, the solvent is awater-ethanol or water-methanol acid buffered solution. In someembodiments, the solvent has a pH of 1.8-3. In some embodiments, thesolvent is buffered with citric acid, the process comprising, betweenthe filtering and evaporating steps, adjusting the solvent to a pH of4-9 using sodium hydroxide. In some embodiments, the solvent comprises100% reverse osmosis water. In some embodiments, the soaking is at atemperature of 5-95° C. In some embodiments, the process comprisesapplying a pressure of 50 kPa-100 MPa to the solvent during the soakingstep. In some embodiments, the process comprises agitating the solventduring the soaking step, wherein the soaking step has a duration of 10minutes to 12 hours. In some embodiments, the psychedelic organism is aplant, animal, fungus, protist, or bacterium. In some embodiments, thefungus comprises Amanita muscaria, Psilocybe cubensis, Psilocybecyanescens, or any combination thereof. In some embodiments, thepsychoactive alkaloids comprise psilocybin, psilocin, baeocystin,norbaeocystin, ibotenic acid or any mixture thereof. In someembodiments, the solvent to biomass ratio is in a range from 1 L:1 kg to50 L:1 kg. In some embodiments, the specified purity is 0.1-10%. In someembodiments, the specified purity is specified as a percentage with aprecision of two decimal places. In some embodiments, the carriercomprises ascorbic acid, silicon dioxide, maltodextrin, gum arabic,microcrystalline cellulose, sodium citrate, sodium benzoate, sodiumphosphate, rice, rice hulls, or any combination of the foregoing. Insome embodiments, the process comprises repeating, using furthersolvent, the soaking and filtering steps for the filtered biomass; andcombining the filtered solvent with the filtered further solvent.

A process for obtaining a purified psychoactive alkaloid solution, theprocess comprising: extracting a psychoactive alkaloid from apsychoactive alkaloid source to obtain a psychoactive alkaloid extract;contacting the psychoactive alkaloid extract with an adsorbent materialto obtain an adsorbed psychoactive alkaloid; and eluting the adsorbedpsychoactive alkaloid using a solvent to obtain a purified psychoactivealkaloid solution, wherein the solvent is water, an organic solvent or acombination thereof, under basic, acidic or neutral pH. In someembodiments, the process comprises prior to the treating step, adding anacid or a base to the psychoactive alkaloid extract. In someembodiments, after adding the acid or base, the psychoactive alkaloidextract has a pH ranging from 2.5-4.5 or from 9-10 respectively. In someembodiments, the acid is selected from the group consisting of aceticacid, adipic acid, ascorbic acid, phosphoric acid, ammonium aluminumsulphate, ammonium citrate dibasic, ammonium citrate monobasic, calciumcitrate, calcium fumarate, calcium gluconate, calcium phosphate dibasic,calcium phosphate, hydrochloric acid, sulphuric acid monobasic, calciumphosphate tribasic, citric acid, fumaric acid, gluconic acid, magnesiumfumarate, malic acid, phosphoric acid, potassium acid tartrate,potassium citrate, potassium fumarate, sodium citrate, sodium fumarate,sodium gluconate, sodium lactate, sodium potassium hexametaphosphate,sodium potassium tartrate, sodium potassium tripolyphosphate, sodiumpyrophosphate tetrabasic, sodium tripolyphosphate, tartaric acid, andany combination therefrom. In some embodiments, the base is selectedfrom the group consisting of ammonium bicarbonate, ammonium carbonate,ammonium hydroxide, calcium acetate, calcium carbonate, calciumchloride, calcium hydroxide, calcium lactate, calcium oxide, calciumphosphate, dibasic, calcium phosphate monobasic, magnesium carbonate,potassium aluminum sulphate, potassium bicarbonate, potassium carbonate,potassium hydroxide, potassium lactate, potassium phosphate, dibasic,potassium pyrophosphate, tetrabasic, potassium phosphate tribasic,potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate,sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate,sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, and any combination therefrom. Insome embodiments, the adsorbent material is a gel resin, a macroporousresin, or a combination thereof. In some embodiments, the macroporousresin is a non-ionic macroporous resin, an ion-exchange macroporousresin, or a combination thereof. In some embodiments, the psychoactivealkaloid source comprises psilocybin, psilocin, baeocystin,norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine,5-MeO-DMT (5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine(DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid,lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine,chanoclavine, or any combination therefrom. In some embodiments, theorganic solvent is selected from a group consisting of C1-4 primaryaliphatic alcohols, C3-4 ketones, and any combination therefrom. In someembodiments, the process comprises further purifying the obtainedpurified psychoactive alkaloid solution by repeating, with the obtainedpurified psychoactive alkaloid solution, the treating step with adifferent adsorbent material and the eluting step with another solvent.In some embodiments, the process comprises evaporating a portion ofsolvent from the purified psychoactive alkaloid solution to obtain apurified psychoactive alkaloid slurry. In some embodiments, the purifiedpsychoactive alkaloid slurry comprises 5% by weight or more of apsychoactive alkaloid. In some embodiments, the process comprisesstandardizing the purified psychoactive alkaloid slurry by addingthereto a quantity of excipient measured to provide a specificconcentration of psychoactive alkaloid when the purified psychoactivealkaloid slurry is dried; and drying the purified psychoactive alkaloidslurry by evaporating the remaining portion of the solvent to obtain astandardized, purified, powdered psychoactive alkaloid extract havingthe specific concentration of psychoactive alkaloid. In someembodiments, the psychoactive alkaloid comprises psilocybin, psilocin,baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin,bufotenidine, 5-MeO-DMT (5-methoxy-N.N-dimethyltryptamine),N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine,muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH),elymoclavine, ergometrinine, chanoclavine, or any combination therefrom;and the standardized, purified, powdered psychoactive alkaloid extracthas a psychoactive alkaloid concentration ranging from 0.1-99% byweight. In some embodiments, the excipient is selected from the groupconsisting of silicon dioxide, ascorbic acid, maltodextrin, gum arabic,microcrystalline cellulose, sodium benzoate, sodium phosphate, sodiumcitrate, rice hulls, rice and any combination therefrom. In someembodiments, the process comprises prior to the treating step: adding anacid to the psychoactive alkaloid extract to bring its pH to 4±0.5; andremoving solids from the psychoactive alkaloid extract; and after thetreating step and before the eluting step: washing the adsorbentmaterial with purified water; wherein: the adsorbent material is anon-ionic macroporous resin; and the solvent used for the eluting stepis a hydro-ethanol solvent. In some embodiments, the hydro-ethanolsolvent is 5% ethanol. In some embodiments, the process comprises priorto the treating step: adding an acid to the psychoactive alkaloidextract to bring its pH to 3±0.5; after the treating step and before theeluting step: washing the adsorbent material with 100% ethanol, whereinthe adsorbent material is a macroporous strong cation exchange resin inan H⁺ or an Na⁺ form; and washing the adsorbent material with purifiedwater; wherein the solvent used for the eluting step is 2% hydrochloricacid and 80% ethanol; and after the eluting step: adding alkali to thepurified psychoactive alkaloid solution to bring its pH to 4±0.5;removing solids from the purified psychoactive alkaloid solution;evaporating a portion of the solvent from the purified psychoactivealkaloid solution; removing further solids from the purifiedpsychoactive alkaloid solution; treating the purified psychoactivealkaloid extract with a non-ionic macroporous resin to obtain a secondadsorbed psychoactive alkaloid; washing the non-ionic macroporous resinwith purified water; and eluting the second adsorbed psychoactivealkaloid from the non-ionic macroporous resin using a hydro-ethanolsolvent to obtain a twice purified psychoactive alkaloid solution. Insome embodiments, the process comprises prior to the treating step:adding a base to the psychoactive alkaloid extract to bring its pH to9.5±0.5; after the treating step and before the eluting step: washingthe adsorbent material with 100% ethanol, wherein the adsorbent materialis a macroporous strong anion exchange resin in an OH⁻ or a Cl⁻ form;and washing the adsorbent material with purified water; wherein thesolvent used for the eluting step is 2% sodium chloride and 80% ethanol;and after the eluting step: adding acid to the purified psychoactivealkaloid solution to bring its pH to 4±0.5; removing solids from thepurified psychoactive alkaloid solution; evaporating a portion of thesolvent from the purified psychoactive alkaloid solution; removingfurther solids from the purified psychoactive alkaloid solution;treating the purified psychoactive alkaloid extract with a non-ionicmacroporous resin to obtain a second adsorbed psychoactive alkaloid;washing the non-ionic macroporous resin with purified water; and elutingthe second adsorbed psychoactive alkaloid from the non-ionic macroporousresin using a hydro-ethanol solvent to obtain a twice purifiedpsychoactive alkaloid solution. In some embodiments, the psychoactivealkaloid source comprises psychoactive fungus and the extracting stepcomprises: drying and pulverizing the psychoactive alkaloid source toobtain a dried biomass; heating the dried biomass in a first solvent toobtain a first slurry, and filtering the first slurry to obtain a firstfiltrate and a first residue; heating the first residue in a secondsolvent to obtain a second slurry, and filtering the second slurry toobtain a second filtrate and a second residue; and mixing the firstfiltrate and the second filtrate to obtain the psychoactive alkaloidextract. In some embodiments, the first solvent and the second solventare selected from a group consisting of a primary aliphatic alcohol, aketone, purified water, and any combination therefrom; and the heatingis carried out at a temperature ranging from 5-95° C. and for a timeduration ranging from 10 minutes to 12 hours. In some embodiments, thepsychoactive alkaloid source is Anadenanthera peregrina, the processcomprising: prior to the treating step: adding an acid to thepsychoactive alkaloid extract to bring its pH to 4±0.5; and removingsolids from the psychoactive alkaloid extract; and after the treatingstep and before the eluting step: washing the adsorbent material withpurified water then with 10% ethanol; wherein: the adsorbent material isa macroporous resin; and the solvent used for the eluting step is 50%ethanol. In some embodiments, the psychoactive alkaloid source comprisesa plant, animal, fungus, protist, or bacterium. In some embodiments, thepsychoactive alkaloid source comprises Psilocybe cyanescens, Psilocybecubensis, Amanita muscaria, or any selection therefrom. In someembodiments, the psychoactive alkaloid source comprises Anadenantheracolubrina or Anadenanthera peregrina. In some embodiments, thepsychoactive alkaloid source comprises Incilius alvarius. In someembodiments, the psychoactive alkaloid source comprises yeast. In someembodiments, the psychoactive alkaloid extract is contacted with theadsorbent material at a flow rate of 1 bed volume per hour (BV/h) to 10BV/h. In some embodiments, the psychoactive alkaloid extract iscontacted with the adsorbent material at a flow rate of 2 bed volumesper hour (BV/h) to 6 BV/h.

A process for obtaining a psychoactive alkaloid extract with a desiredamount of a phosphorylated psychoactive alkaloid and a desired amount ofa dephosphorylated psychoactive alkaloid, the process comprising: dryingand pulverizing a psychoactive alkaloid source to obtain a driedpowdered biomass; extracting a psychoactive alkaloid from the driedpowdered biomass with an acidified solvent or a basified solvent toobtain a psychoactive alkaloid liquid with a specific pH, wherein thespecific pH is lower than 3.5 or greater than 10.5; adjusting the pH ofthe psychoactive alkaloid liquid to a pH ranging from 3.5-4.5; andevaporating the solvent from the psychoactive alkaloid liquid to obtainthe psychoactive alkaloid extract with the desired amount of thephosphorylated psychoactive alkaloid and the desired amount of thedephosphorylated psychoactive alkaloid; wherein: the desired amount ofthe phosphorylated psychoactive alkaloid is 0-100% by weight of a totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract; and the desired amount of the dephosphorylatedpsychoactive alkaloid is the remainder of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Insome embodiments, the phosphorylated alkaloid is psilocybin, baeocystin,norbaeocystin, aeruginascin, or any combination therefrom; and thedephosphorylated alkaloid is psilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination therefrom. Insome embodiments, the psychoactive alkaloid source comprises psilocybin,baeocystin, norbaeocystin, aeruginascin, psilocin, norpsilocin,4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine, or anycombination therefrom. In some embodiments, the extracting stepcomprises: mixing the dried powdered biomass with the acidified solventor the basified solvent to obtain a slurry; and filtrating the slurry toobtain a filtrate residue and the psychoactive alkaloid liquid. In someembodiments, the extracting step comprises further extracting thepsychoactive alkaloid by repeating, with the obtained filtrate residue,the extracting step with the same or a different acidified solvent, orthe same or a different basified solvent. In some embodiments, after themixing step the acidified solvent or the basified solvent, the slurryhas a pH ranging from 0.5-3.5 or from 10.5-13.5 respectively. In someembodiments, the acidified solvent is a mixture of an acid; and a C1-C4primary aliphatic alcohol, a C3-C4 ketone, water, or any combinationselected therefrom. In some embodiments, the basified solvent is amixture of a base; and a C1-C4 primary aliphatic alcohol, a C3-C4ketone, water, or any combination selected therefrom. In someembodiments, the extraction is performed: at a temperature ranging from5-95° C.; and for a time period ranging from 10-720 minutes. In someembodiments, the extraction is performed at a pressure ranging from 50kPa-138 MPa (7 to 20,000 psi). In some embodiments, the extraction isperformed with a solvent to solid proportion of 1 L:1 kg to 50 L:1 kg,wherein the solid is the dried powdered biomass. In some embodiments,the specific pH is lower than 3.5, and the desired amount of thephosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is 100% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Insome embodiments, the specific pH is greater than 10.5, and the desiredamount of the phosphorylated psychoactive alkaloid is 100% by weight ofthe total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid extract, and the desired amount of thedephosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract. In some embodiments, the specific pH is greater than10.5, and a maximum desired amount of the phosphorylated alkaloid islimited by an amount of the dephosphorylated alkaloid in thepsychoactive alkaloid source. In some embodiments, the specific pH isgreater than 10.5, and the desired amount of the phosphorylatedpsychoactive alkaloid is 1-99% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Insome embodiments, the process comprises pausing the evaporating stepwhen a portion of the solvent has been evaporated from the psychoactivealkaloid liquid to obtain a psychoactive alkaloid slurry; standardizingthe psychoactive alkaloid slurry by adding thereto a measured quantityof one or more excipients to obtain a standardized slurry with aspecific amount of psychoactive alkaloid content; and continuing theevaporating step by drying the standardized slurry to obtain apsychoactive alkaloid composition comprising the psychoactive alkaloidextract, and one or more excipients; wherein a total psychoactivealkaloid content in the psychoactive alkaloid composition is specifiedas a result of the standardizing step. In some embodiments, the desiredamount of the phosphorylated psychoactive alkaloid is 100% by weight ofthe total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid composition, the process comprising: preparinganother psychoactive alkaloid composition comprising anotherpsychoactive alkaloid extract of some embodiments disclosed hereinwherein the desired amount of the dephosphorylated psychoactive alkaloidis 100% by weight of the total phosphorylatable psychoactive alkaloidcontent in the other psychoactive alkaloid extract; mixing thepsychoactive alkaloid composition and the other psychoactive compositionin a measured ratio to obtain a psychoactive alkaloid compositioncomprising the phosphorylated psychoactive alkaloid of the psychoactivealkaloid composition and the dephosphorylated psychoactive alkaloid ofthe other psychoactive alkaloid composition in a specific ratio; whereinthe specific ratio of phosphorylated psychoactive alkaloid todephosphorylated psychoactive alkaloid ranges from 1:1000 to 1000:1.

A process for obtaining a psychoactive alkaloid composition with aspecific ratio of a phosphorylated psychoactive alkaloid to adephosphorylated psychoactive alkaloid, the process comprising:extracting a psychoactive alkaloid from a dried powdered biomass with abasified solvent to obtain a psychoactive alkaloid liquid with a pHgreater than 10.5, wherein a majority of a total phosphorylatablepsychoactive alkaloid content is the phosphorylated alkaloid and aremainder thereof is the dephosphorylated alkaloid; adjusting the pH ofthe psychoactive alkaloid liquid to a pH ranging from 3.5-4.5;extracting another psychoactive alkaloid from another dried powderedbiomass with an acidified solvent to obtain another psychoactivealkaloid liquid with a pH lower than 3.5, wherein all of a totalphosphorylatable psychoactive alkaloid is the dephosphorylated alkaloid;adjusting the pH of the other psychoactive alkaloid liquid to a pHranging from 3.5-4.5; evaporating a portion of the basified solvent fromthe psychoactive alkaloid liquid and a portion of the acidified solventfrom the other psychoactive alkaloid liquid to obtain a psychoactivealkaloid extract slurry and another psychoactive alkaloid extract slurryrespectively; mixing measured portions of the psychoactive alkaloidextract slurry and the other psychoactive alkaloid extract slurry toobtain a bulk psychoactive alkaloid extract slurry comprising thephosphorylated psychoactive alkaloid and the dephosphorylatedpsychoactive alkaloid in the specific ratio; standardizing the bulkpsychoactive alkaloid extract slurry by adding thereto a measuredquantity of one or more excipients to obtain a standardized bulk slurry;and drying the standardized bulk psychoactive alkaloid slurry to obtainthe psychoactive alkaloid composition, wherein the phosphorylatedpsychoactive alkaloid and the dephosphorylated psychoactive alkaloid arein the specific ratio; wherein the specific ratio of phosphorylatedpsychoactive alkaloid to dephosphorylated psychoactive alkaloid rangesfrom 1:1000 to 1000:1. A psychoactive alkaloid composition comprising: apsychoactive alkaloid extract comprising a desired amount of aphosphorylated psychoactive alkaloid and a desired amount of adephosphorylated psychoactive alkaloid, wherein: the desired amount ofthe phosphorylated psychoactive alkaloid is 0-100% by weight of a totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is the remainder of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract; andone or more excipients. In some embodiments, the composition is inpowder form. In some embodiments, the desired amount of thephosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is 100% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Insome embodiments, the desired amount of the phosphorylated psychoactivealkaloid is 100% by weight of the total phosphorylatable psychoactivealkaloid content in the psychoactive alkaloid extract, and the desiredamount of the dephosphorylated psychoactive alkaloid is 0% by weight ofthe total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid extract. In some embodiments, the phosphorylatedalkaloid is psilocybin, baeocystin, norbaeocystin, aeruginascin, or anycombination selected therefrom; and the dephosphorylated alkaloid ispsilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination selectedtherefrom.

A psychoactive alkaloid composition with a specific ratio of aphosphorylated psychoactive alkaloid and a dephosphorylated psychoactivealkaloid, the composition comprising: a psychoactive alkaloid extracthaving a total phosphorylatable psychoactive alkaloid content of 100% ofa phosphorylated psychoactive alkaloid; another psychoactive alkaloidextract having a total phosphorylatable psychoactive alkaloid content of100% of a dephosphorylated psychoactive alkaloid; and one or moreexcipients; wherein the psychoactive alkaloid extract and the otherpsychoactive alkaloid extract are present in a proportion such that thespecific ratio of phosphorylated psychoactive alkaloid to phosphorylatedpsychoactive alkaloid ranges from 1:1000 to 1000:1.

The present invention is directed to an extraction process ofpsychoactive compounds from psychedelic fungus, for example, thePsilocybe cubensis species of psychedelic mushroom. The principalpsychoactive compounds in Psilocybe cubensis include psilocybin andpsilocin. In particular, the extraction process of psychoactivecompounds involves drying fresh Psilocybe cubensis, followed bygrinding, extraction with a solvent in one or more steps, one or moresteps of filtration, optional adjustment of the pH if the solvent isacidic (acid/water/alcohol) or alkaline (base/water/alcohol),evaporation of the solvent, and standardization. Optionally, the processincludes drying to result in a final powdered psilocybin mushroomextract.

The invention described here consists of a never-before-described methodto produce high-efficiency, standardized preparations of the targetcompounds all while using acceptable solvent systems.

The drying of fresh fungal biomass done in a fashion that does notgreatly reduce the natural psilocybin, psilocin, or baeocystinconcentrations.

The temperature of extraction is between 5 and 95° C. and uses a 1 to50:1 solvent:solid ratio of extraction. Time of extraction from 10 to720 minutes. Pressure may be applied, ranging from 50 kPa to 137 MPa(0.5 atm to 20,000 psi). Multiple species of Psilocybe mushrooms may beused.

Disclosed herein is a process for forming an extract of psychoactivealkaloids from psychoactive organisms such as psychedelic funguscomprising the steps of: soaking a biomass of dried, raw psychedelicfungus in a solvent selected from the group consisting of water-ethanoland water-methanol mixture in order to dissolve the psychoactivealkaloids in the solvent; filtering an undissolved portion of thebiomass from the solvent; evaporating the solvent to remove the methanolor ethanol completely, leaving a concentrated slurry or a residue thatis converted to the concentrated slurry by adding water thereto: andstandardizing the concentrated slurry by adding thereto a quantity ofcarrier measured to achieve a specified purity of extract. In someembodiments the solvent is water-methanol. In some embodiments thesolvent is water-methanol, the concentration being a trace to about100%. In some embodiments the solvent is water-methanol, about 10% toabout 90%. In some embodiments the solvent is water-methanol, about 20%to about 80%. In some embodiments the solvent is water-methanol, about30% to about 70%. In some embodiments the solvent is water-methanol,about 40% to about 60%. In some embodiments the solvent iswater-methanol, about 50% to about 50%. In some embodiments the solventis water-methanol, about 60% to about 40%. In some embodiments thesolvent is water-methanol, about 70% to about 30%. In some embodimentsthe solvent is water-methanol, about 80% to about 20%. In someembodiments the solvent is water-methanol, about 90% to about 10%. Insome embodiments the solvent is water-methanol, about 100% to a trace.In some embodiments the solvent is water-ethanol. In some embodimentsthe solvent is water-ethanol, the concentration being a trace to about100%. In some embodiments the solvent is water-ethanol, about 10% toabout 90%. In some embodiments the solvent is water-ethanol, about 20%to about 80%. In some embodiments the solvent is water-ethanol, about30% to about 70%. In some embodiments the solvent is water-ethanol,about 40% to about 60%. In some embodiments the solvent iswater-ethanol, about 50% to about 50%. In some embodiments the solventis water-ethanol, about 60% to about 40%. In some embodiments thesolvent is water-ethanol, about 70% to about 30%. In some embodimentsthe solvent is water-ethanol, about 80% to about 20%. In someembodiments the solvent is water-ethanol, about 90% to about 10%. Insome embodiments the solvent is water-ethanol, about 100% to a trace. Insome embodiments, the standardizing comprises measuring a psychoactivealkaloid content in the concentrated slurry, and using the psychoactivealkaloid content, the specified purity and a volume of the concentratedslurry to determine the quantity of carrier.

The present invention relates to a process for obtaining a purifiedpsychoactive alkaloid solution from a psychoactive alkaloid source. Thepurification process of the present invention allows for producingstandardized preparations of psychoactive alkaloids, all while usingacceptable solvent and processing systems.

Standardization is a method that can be used to solve the problem ofinconsistency in the finished product. However, when dealing with alow-potency feedstock material, it may be difficult to standardize theactive ingredients to a high percentage content and achieve the desiredtherapeutic effects. We therefore need to concentrate the activeingredients beforehand, using a purification process. It may also bedesirable to concentrate the active ingredients to a high enough degreethat the resulting volume of the final product is limited for a specificapplication, such as to fit into a standard size two-piece capsule.

A psychoactive alkaloid source is used to provide a psychoactivealkaloid extract. The source may be a species containing psychedelicalkaloids or a prior extract therefrom. Psychoactive alkaloids in theextract are adsorbed onto a resin or other adsorbent material, fromwhich they are then eluted to provide a purified psychoactive alkaloidsolution. The process may be repeated with different resins, differentpH values, and different elution solvents. Solids present in the extractmay be removed at various stages by filtering or centrifuging.

The purification process of the present invention allows for purifyingrelatively low-potency feedstocks to result in a purified psychoactivealkaloid solution that may have a relatively high concentration ofpsychoactive alkaloid. Depending on the embodiment, the process may be apurification process that enriches the psychoactive alkaloid content ofthe final formulation compared to the alkaloid content in the rawmaterials. Purification may also be the removal of some of theimpurities, irrespective of the final alkaloid content. The process ofpurification in the present invention allows use of the lowest-grade rawmaterials to obtain a product capable of standardization to a desiredspecification.

The purification process of the present invention may be, depending onthe embodiment, a relatively simple and robust psychoactive alkaloidpurification process, which is suitable for the production offood-grade, nutraceutical-grade, or pharmaceutical-grade standardizedextracts, especially of psilocybin, psilocin, baeocystin, norbaeocystin,norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT(5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine(LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acidhydroxyethylamide (LSH), elymoclavine, ergometrinine, and/orchanoclavine.

The present invention also relates to a standardization process forpreparation of standardized extracts of psychoactive alkaloids. Thestandardization process of the present invention allows forstandardizing the purified psychoactive alkaloid solution to result in apurified psychoactive alkaloid extract with a specific concentration ofpsychoactive alkaloids. The standardization process of the presentinvention may also be a simple and cost-efficient process.

The standardized psychoactive alkaloid extracts of the present inventioncan be used in, for example, medical research on the use of psychedelicsubstances as treatments for addiction, post-traumatic stress disorder,depression, cluster headaches, and other illnesses. They may also beused in traditional entheogenic practices or consumed recreationallywhere such activity is permitted by law.

Disclosed herein is a process for obtaining a purified psychoactivealkaloid solution, the process comprising: extracting a psychoactivealkaloid from a psychoactive alkaloid source to obtain a psychoactivealkaloid extract; treating the psychoactive alkaloid extract with anadsorbent material to obtain an adsorbed psychoactive alkaloid; andeluting the adsorbed psychoactive alkaloid using a solvent to obtain apurified psychoactive alkaloid solution, wherein the solvent is water,an organic solvent or a combination thereof, under basic, acidic orneutral pH.

In some embodiments, the process includes: evaporating a portion ofsolvent from the purified psychoactive alkaloid solution to obtain aconcentrated slurry; standardizing the concentrated slurry by addingthereto a quantity of excipient measured to provide a specificconcentration of psychoactive alkaloid when the concentrated slurry isdried; and drying the slurry by evaporating the remaining portion of thesolvent to obtain a standardized, purified, powdered psychoactivealkaloid extract having the specific concentration of psychoactivealkaloid.

An aim of the invention is to standardize the amount of psychoactivealkaloid present in the composition. Depending on the embodiment and thespecific types of excipient added, a secondary, optional aspect of theinvention is the provision of a psychoactive alkaloid extract in theform of a dry, flowable and shelf-stable powder. The powder may be usedas a dietary supplement or medicine and can be added to various edibleproducts, tablets, or capsules, or it may be used for medical research,including the study of the treatment of mental illnesses.

By increasing the active alkaloid concentration through extraction andthen titrating back to a lower, standardized alkaloid concentration, theproduct achieves consistency in bioactive content from lot to lot. Bythe addition of specific types of excipient, flowability and stabilitymay also be improved in the composition, as compared to the extract.

A useful formulation needs to contain a minimum amount of the activeingredient and also be of an acceptable total size. For example, apsilocybin dose might be 25 mg. If this is required in a single capsuleand the powder has a concentration of the active ingredient of only 1%,then 2500 mg of powder would be needed. This would be too much for asingle capsule. However, if the extract can be concentrated to approx.15%, then there is room to add an excipient to get it down to say, arepeatable 10%, which now means that only 250 mg of powder is needed inthe capsule, which is an acceptable size.

While the concentration of psychoactive alkaloid in the composition may,in some embodiments, be lower than that found in some of the source rawmaterial (mushrooms or seeds for example), it is a known concentration,which can be stable from batch to batch, eliminating the variabilityfound in the natural sources. This allows for control andstandardization of the dose, even if it is lower than some of the rawmaterials themselves.

Disclosed herein is a psychoactive alkaloid composition consistingessentially of, by weight: 0.1-99.9% of a psychoactive alkaloid extract;one or more preservatives up to 10%, a flow agent up to 2%, or both theone or more preservatives up to 10% and the flow agent up to 2%; and0-94% of a carrier.

The inventors have realized that there are occasions where it would bebeneficial to control, either by halting or promoting, the conversion ofphosphorylated alkaloids such as psilocybin during extraction and anysubsequent purification process. For example, there may be occasionswhere extracts with phosphorylated psychoactive alkaloids as the only ormajority of the total psychoactive alkaloid in the extract are required.Likewise, there may be occasions where extracts with dephosphorylatedpsychoactive alkaloids as the only or majority of the total psychoactivealkaloid in the extract are required.

For example, the alkaloid in the psychoactive extract may be entirelypsilocin, resulting from promotion of the conversion, or all or mostlypsilocybin, from the halting or inhibition of the conversion. There willlikely, but not necessarily, be some psilocin present in the processwhere the conversion is halted, as the harvesting of the mushrooms canoften cause unavoidable conversion into psilocin.

Controlling the promotion or inhibition of dephosphorylation of theaforementioned alkaloids to result in a psychoactive alkaloid extractwith a specific desired content of both phosphorylated anddephosphorylated psychoactive alkaloid has not been seen in the industryor academia to date. Likewise, compositions resulting from such controlhave not yet been seen.

Thus, there is a need in the art of a process for controlling thedephosphorylation of the aforementioned alkaloids to result in apsychoactive alkaloid extract with specific desired amounts ofphosphorylated and dephosphorylated psychoactive alkaloid. Also requiredin the art is a psychoactive alkaloid composition having an accuratepsychoactive alkaloid content, with specific desired amounts ofphosphorylated and dephosphorylated psychoactive alkaloid.

Disclosed herein is a process for obtaining a psychoactive alkaloidextract with a desired amount of a phosphorylated psychoactive alkaloidand a desired amount of a dephosphorylated psychoactive alkaloid, theprocess comprising: drying and pulverizing a psychoactive alkaloidsource to obtain a dried powdered biomass; extracting a psychoactivealkaloid from the dried powdered biomass with an acidified solvent or abasified solvent to obtain a psychoactive alkaloid liquid with aspecific pH, wherein the specific pH is lower than 3.5 or greater than10.5; adjusting the pH of the psychoactive alkaloid liquid to a pHranging from 3.5-4.5; and evaporating the solvent from the psychoactivealkaloid liquid to obtain the psychoactive alkaloid extract with thedesired amount of the phosphorylated psychoactive alkaloid and thedesired amount of the dephosphorylated psychoactive alkaloid; wherein:the desired amount of the phosphorylated psychoactive alkaloid is 0-100%by weight of a total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract; and the desired amount of thedephosphorylated psychoactive alkaloid is the remainder of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract.

Also disclosed is a process for obtaining a psychoactive alkaloidcomposition with a specific ratio of a phosphorylated psychoactivealkaloid to a dephosphorylated psychoactive alkaloid, the processcomprising: extracting a psychoactive alkaloid from a dried powderedbiomass with a basified solvent to obtain a psychoactive alkaloid liquidwith a pH greater than 10.5, wherein a majority of a totalphosphorylatable psychoactive alkaloid content is the phosphorylatedalkaloid and a remainder thereof is the dephosphorylated alkaloid;adjusting the pH of the psychoactive alkaloid liquid to a pH rangingfrom 3.5-4.5; extracting another psychoactive alkaloid from anotherdried powdered biomass with an acidified solvent to obtain anotherpsychoactive alkaloid liquid with a pH lower than 3.5, wherein all of atotal phosphorylatable psychoactive alkaloid is the dephosphorylatedalkaloid; adjusting the pH of the other psychoactive alkaloid liquid toa pH ranging from 3.5-4.5; evaporating a portion of the basified solventfrom the psychoactive alkaloid liquid and a portion of the acidifiedsolvent from the other psychoactive alkaloid liquid to obtain apsychoactive alkaloid extract slurry and another psychoactive alkaloidextract slurry respectively; mixing measured portions of thepsychoactive alkaloid extract slurry and the other psychoactive alkaloidextract slurry to obtain a bulk psychoactive alkaloid extract slurrycomprising the phosphorylated psychoactive alkaloid and thedephosphorylated psychoactive alkaloid in the specific ratio;standardizing the bulk psychoactive alkaloid extract slurry by addingthereto a measured quantity of one or more excipients to obtain astandardized bulk slurry; and drying the standardized bulk psychoactivealkaloid slurry to obtain the psychoactive alkaloid composition, whereinthe phosphorylated psychoactive alkaloid and the dephosphorylatedpsychoactive alkaloid are in the specific ratio; wherein the specificratio of phosphorylated psychoactive alkaloid to dephosphorylatedpsychoactive alkaloid ranges from 1:1000 to 1000:1.

Further disclosed is a psychoactive alkaloid composition comprising: apsychoactive alkaloid extract comprising a desired amount of aphosphorylated psychoactive alkaloid and a desired amount of adephosphorylated psychoactive alkaloid, wherein: the desired amount ofthe phosphorylated psychoactive alkaloid is 0-100% by weight of a totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is the remainder of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract; andone or more excipients.

Still further disclosed is a psychoactive alkaloid composition with aspecific ratio of a phosphorylated psychoactive alkaloid and adephosphorylated psychoactive alkaloid, the composition comprising: apsychoactive alkaloid extract having a total phosphorylatablepsychoactive alkaloid content of 100% of a phosphorylated psychoactivealkaloid; another psychoactive alkaloid extract having a totalphosphorylatable psychoactive alkaloid content of 100% of adephosphorylated psychoactive alkaloid; and one or more excipients;wherein the psychoactive alkaloid extract and the other psychoactivealkaloid extract are present in a proportion such that the specificratio of phosphorylated psychoactive alkaloid to phosphorylatedpsychoactive alkaloid ranges from 1:1000 to 1000:1.

A method for generating a psychoactive alkaloid extract comprising 0.1%to 99% by weight of a psychoactive alkaloid from a psychoactiveorganism, the method comprising: providing a biomass of the psychoactiveorganism; contacting the biomass with 10 to 100 milliliters (mL) ofsolvent per gram (g) of the biomass; and evaporating the solvent fromthe biomass to yield the psychoactive alkaloid extract comprising 0.1%to 99% by weight of the psychoactive alkaloid. In some embodiments,following (b), the biomass is contacted with a second solvent. In someembodiments, the solvent is selected from 100% methanol, analcohol:water mixture wherein the alcohol comprises 60% to 99% of thealcohol:water mixture, an alcohol:acid mixture wherein the alcoholcomprises 60% to 99% of the alcohol:acid mixture, an alcohol:basemixture wherein the alcohol comprises 60% to 99% of the alcohol:basemixture, an alcohol:water mixture wherein the alcohol comprises 70% to80% of the alcohol:water mixture, an alcohol:acid mixture wherein thealcohol comprises 70% to 80% of the alcohol:acid mixture, analcohol:base mixture wherein the alcohol comprises 70% to 80% of thealcohol:base mixture, acidified water, and basified water. In someembodiments, the alcohol of the alcohol:water mixture, the alcohol:acidmixture, or alcohol:base mixture, is a C1-C4 primary aliphatic alcohol.In some embodiments, the C1-C4 primary aliphatic alcohol is ethanol ormethanol. In some embodiments, the solvent is buffered to a pH of either4 or less, or 9 or greater. In some embodiments, the solvent has a pH of10 or greater and the psychoactive alkaloid extract comprises greaterthan 50% of a phosphorylated psychoactive alkaloid. In some embodiments,the solvent has a pH of 4 or less and the psychoactive alkaloid extractcomprises greater than 50% of a dephosphorylated psychoactive alkaloid.In some embodiments, the solvent is buffered with ammonium bicarbonate,ammonium carbonate, ammonium hydroxide, calcium acetate, calciumcarbonate, calcium chloride, calcium hydroxide, calcium lactate, calciumoxide, calcium phosphate, dibasic, calcium phosphate monobasic,magnesium carbonate, potassium aluminum sulphate, potassium bicarbonate,potassium carbonate, potassium hydroxide, potassium lactate, potassiumphosphate, dibasic, potassium pyrophosphate, tetrabasic, potassiumphosphate tribasic, potassium tripolyphosphate, sodium acetate, sodiumacid pyrophosphate, sodium aluminum phosphate, sodium aluminum sulphate,sodium bicarbonate, sodium bisulphate, sodium carbonate, sodiumhexametaphosphate, sodium hydroxide, sodium lactate, sodium phosphatedibasic, sodium phosphate monobasic, sodium phosphate tribasic, and anycombination thereof. In some embodiments, the solvent is buffered withacetic acid, adipic acid, ascorbic acid, phosphoric acid, ammoniumaluminum sulphate, ammonium citrate dibasic, ammonium citrate monobasic,calcium citrate, calcium fumarate, calcium gluconate, calcium phosphatedibasic, calcium phosphate, hydrochloric acid, sulphuric acid monobasic,calcium phosphate tribasic, citric acid, fumaric acid, gluconic acid,magnesium fumarate, malic acid, phosphoric acid, potassium acidtartrate, potassium citrate, potassium fumarate, sodium citrate, sodiumfumarate, sodium gluconate, sodium lactate, sodium potassiumhexametaphosphate, sodium potassium tartrate, sodium potassiumtripolyphosphate, sodium pyrophosphate tetrabasic, sodiumtripolyphosphate, tartaric acid, and any combination thereof. In someembodiments, the psychoactive organism is Psilocybe cyanescens,Psilocybe cubensis, Amanita muscaria, or any selection thereof. In someembodiments, the psychoactive alkaloid is psilocybin, psilocin,baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin,bufotenidine, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine),N,N-dimethyltryptamine (DMT), 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine ergine (LSA), ergonovine,ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide(LSH), elymoclavine, ergometrinine, and/or chanoclavine, or anycombination thereof.

A method for generating a phosphorylated psychoactive alkaloid extractcomprising 0.1% to 99% by weight of a psychoactive alkaloid from apsychoactive organism, the method comprising: providing a biomass of thepsychoactive organism; contacting the biomass with 10 to 100 milliliters(mL) of solvent per gram (g) of the biomass wherein the solvent has a pHof 9 or greater and the psychoactive alkaloid comprises greater than 50%of a phosphorylated psychoactive alkaloid; and evaporating the solventfrom the biomass to yield the phosphorylated psychoactive alkaloidextract comprising 0.1% to 99% by weight of the psychoactive alkaloid.In some embodiments, following (b), the biomass is contacted with asecond solvent. In some embodiments, the solvent is selected from 100%methanol, an alcohol:water mixture wherein the alcohol comprises 60% to99% of the alcohol:water mixture, an alcohol:acid mixture wherein thealcohol comprises 60% to 99% of the alcohol:acid mixture, analcohol:base mixture wherein the alcohol comprises 60% to 99% of thealcohol:base mixture, an alcohol:water mixture wherein the alcoholcomprises 70% to 80% of the alcohol:water mixture, an alcohol:acidmixture wherein the alcohol comprises 70% to 80% of the alcohol:acidmixture, an alcohol:base mixture wherein the alcohol comprises 70% to80% of the alcohol:base mixture, acidified water, and basified water. Insome embodiments, the alcohol of the alcohol:water mixture, thealcohol:acid mixture, or the alcohol:base mixture, is a C1-C4 primaryaliphatic alcohol. In some embodiments, the C1-C4 primary aliphaticalcohol is ethanol or methanol. In some embodiments, the solvent isbuffered with ammonium bicarbonate, ammonium carbonate, ammoniumhydroxide, calcium acetate, calcium carbonate, calcium chloride, calciumhydroxide, calcium lactate, calcium oxide, calcium phosphate, dibasic,calcium phosphate monobasic, magnesium carbonate, potassium aluminumsulphate, potassium bicarbonate, potassium carbonate, potassiumhydroxide, potassium lactate, potassium phosphate, dibasic, potassiumpyrophosphate, tetrabasic, potassium phosphate tribasic, potassiumtripolyphosphate, sodium acetate, sodium acid pyrophosphate, sodiumaluminum phosphate, sodium aluminum sulphate, sodium bicarbonate, sodiumbisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, and any combination thereof. Insome embodiments, the solvent is buffered with acetic acid, adipic acid,ascorbic acid, phosphoric acid, ammonium aluminum sulphate, ammoniumcitrate dibasic, ammonium citrate monobasic, calcium citrate, calciumfumarate, calcium gluconate, calcium phosphate dibasic, calciumphosphate, hydrochloric acid, sulphuric acid monobasic, calciumphosphate tribasic, citric acid, fumaric acid, gluconic acid, magnesiumfumarate, malic acid, phosphoric acid, potassium acid tartrate,potassium citrate, potassium fumarate, sodium citrate, sodium fumarate,sodium gluconate, sodium lactate, sodium potassium hexametaphosphate,sodium potassium tartrate, sodium potassium tripolyphosphate, sodiumpyrophosphate tetrabasic, sodium tripolyphosphate, tartaric acid, andany combination thereof. In some embodiments, the psychoactive organismis Psilocybe cyanescens, Psilocybe cubensis, Amanita muscaria, or anyselection thereof. In some embodiments, the phosphorylated psychoactivealkaloid is psilocybin, baeocystin, norbaeocystin, aeruginascin, or anycombination thereof.

A method for generating a dephosphorylated psychoactive alkaloid extractcomprising 0.1% to 99% by weight of a psychoactive alkaloid from apsychoactive organism, the method comprising: providing a biomass of thepsychoactive organism; contacting the biomass with 10 to 100 milliliters(mL) of solvent per gram (g) of the biomass wherein the solvent has a pHof 4 or less and the psychoactive alkaloid comprises greater than 50% ofa dephosphorylated psychoactive alkaloid; and evaporating the solventfrom the biomass to yield the dephosphorylated psychoactive alkaloidextract comprising 0.1% to 99% by weight of the psychoactive alkaloid.In some embodiments, following (b), the biomass is contacted with asecond solvent. In some embodiments, the solvent is selected from 100%methanol, an alcohol:water mixture wherein the alcohol comprises 60% to99% of the alcohol:water mixture, an alcohol:acid mixture wherein thealcohol comprises 60% to 99% of the alcohol:acid mixture, analcohol:base mixture wherein the alcohol comprises 60% to 99% of thealcohol:base mixture, an alcohol:water mixture wherein the alcoholcomprises 70% to 80% of the alcohol:water mixture, an alcohol:acidmixture wherein the alcohol comprises 70% to 80% of the alcohol:acidmixture, an alcohol:base mixture wherein the alcohol comprises 70% to80% of the alcohol:base mixture, acidified water, and basified water. Insome embodiments, the alcohol of the alcohol:water mixture, thealcohol:acid mixture, or the alcohol:base mixture, is a C1-C4 primaryaliphatic alcohol. In some embodiments, the C1-C4 primary aliphaticalcohol is ethanol or methanol. In some embodiments, the solvent isbuffered with ammonium bicarbonate, ammonium carbonate, ammoniumhydroxide, calcium acetate, calcium carbonate, calcium chloride, calciumhydroxide, calcium lactate, calcium oxide, calcium phosphate, dibasic,calcium phosphate monobasic, magnesium carbonate, potassium aluminumsulphate, potassium bicarbonate, potassium carbonate, potassiumhydroxide, potassium lactate, potassium phosphate, dibasic, potassiumpyrophosphate, tetrabasic, potassium phosphate tribasic, potassiumtripolyphosphate, sodium acetate, sodium acid pyrophosphate, sodiumaluminum phosphate, sodium aluminum sulphate, sodium bicarbonate, sodiumbisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, and any combination thereof. Insome embodiments, the solvent is buffered with acetic acid, adipic acid,ascorbic acid, phosphoric acid, ammonium aluminum sulphate, ammoniumcitrate dibasic, ammonium citrate monobasic, calcium citrate, calciumfumarate, calcium gluconate, calcium phosphate dibasic, calciumphosphate, hydrochloric acid, sulphuric acid monobasic, calciumphosphate tribasic, citric acid, fumaric acid, gluconic acid, magnesiumfumarate, malic acid, phosphoric acid, potassium acid tartrate,potassium citrate, potassium fumarate, sodium citrate, sodium fumarate,sodium gluconate, sodium lactate, sodium potassium hexametaphosphate,sodium potassium tartrate, sodium potassium tripolyphosphate, sodiumpyrophosphate tetrabasic, sodium tripolyphosphate, tartaric acid, andany combination thereof. In some embodiments, the psychoactive organismis Psilocybe cyanescens, Psilocybe cubensis, Amanita muscaria, or anyselection thereof. In some embodiments, the dephosphorylatedpsychoactive alkaloid is psilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination thereof.

This summary does not necessarily describe all features of theinvention, and different embodiments thereof may provide at least onebut not necessarily all of the benefits described herein.

BRIEF DESCRIPTION OF DRAWINGS

The following drawings illustrate embodiments of the invention, whichshould not be construed as restricting the scope of the invention in anyway.

FIG. 1 is a high-level flowchart showing the key steps of a process forextracting psychoactive alkaloids from psychedelic fungus, according toan embodiment of the present invention.

FIG. 2 is a flowchart showing more detailed steps of a process forextracting psychoactive alkaloids from Psilocybe cubensis using a 75%ethanol solvent, according to an embodiment of the present invention.

FIG. 3 is a flowchart showing more detailed steps of a process forextracting psychoactive alkaloids from Psilocybe cubensis using ahydro-ethanol solvent, according to an embodiment of the presentinvention.

FIG. 4 is a flowchart showing more detailed steps of a process forextracting psychoactive alkaloids from Psilocybe cubensis using a watersolvent, according to an embodiment of the present invention.

FIG. 5 is a flowchart showing more detailed steps of a process forextracting psychoactive alkaloids from Psilocybe cyanescens using amethanol solvent, according to an embodiment of the present invention.

FIG. 6 is a flowchart showing more detailed steps of a process forextracting psychoactive alkaloids from Psilocybe cubensis using abuffered acidic solvent, according to an embodiment of the presentinvention.

FIG. 7 is a flowchart showing more detailed steps of a process forextracting psychoactive alkaloids Psilocybe cubensis using a bufferedalkaline solvent, according to an embodiment of the present invention.

FIG. 8 is a schematic diagram of the apparatus used for the extractionof psychoactive compounds according to an embodiment of the presentinvention.

FIG. 9 illustrates the steps of a basic process for obtaining a purifiedpsychoactive alkaloid solution, according to an embodiment of thepresent invention.

FIG. 10 illustrates in detail the basic and optional steps of a processfor purification of a psychoactive alkaloid extract, according to anembodiment of the present invention.

FIG. 11 illustrates a process for standardizing a purified psychoactivealkaloid solution to obtain a standardized psychoactive alkaloidextract, according to an embodiment of the present invention.

FIG. 12 illustrates detailed steps of a process for extractingpsychoactive alkaloids from Psilocybe cubensis, according to anembodiment of the present invention.

FIG. 13 is a schematic diagram of an apparatus used for obtaining apurified psychoactive alkaloid solution and standardizing the same toresult in a standardized psychoactive alkaloid extract, according to anembodiment of the present invention.

FIG. 14 illustrates steps of a process for obtaining a standardizedpsychoactive alkaloid composition, according to an embodiment of thepresent invention.

FIG. 15 illustrates a process for extracting psychoactive alkaloid fromPsilocybe cubensis, according to an embodiment of the present invention.

FIG. 16 illustrates detailed steps of a process for purifyingpsychoactive alkaloid from Psilocybe cubensis, according to anembodiment of the present invention.

FIG. 17 is a schematic diagram of the apparatus used for obtaining apsychoactive alkaloid composition, according to an embodiment of thepresent invention.

FIG. 18 illustrates the key steps of a process for obtaining apsychoactive alkaloid extract with dephosphorylation control, accordingto an embodiment of the present invention.

FIG. 19 illustrates in detailed steps of a process for obtaining apsychoactive alkaloid extract with dephosphorylation control, accordingto an embodiment of the present invention.

FIG. 20 illustrates a process for standardizing a psychoactive alkaloidextract to obtain a standardized psychoactive alkaloid extract.

FIG. 21 illustrates a process for obtaining a psychoactive alkaloidcomposition with a specific ratio of a phosphorylated psychoactivealkaloid to a dephosphorylated psychoactive alkaloid, according to anembodiment of the present invention.

FIG. 22 illustrates detailed steps of a process for obtaining apsychoactive alkaloid composition with a specific ratio of aphosphorylated psychoactive alkaloid to a dephosphorylated psychoactivealkaloid, according to another embodiment of the present invention.

FIG. 23 illustrates a schematic diagram of the apparatus used forobtaining a psychoactive alkaloid extract and standardizing the same toresult in a standardized psychoactive alkaloid extract, according to anembodiment of the present invention.

FIG. 24 is a chart demonstrating a relationship between solvent to solidratio and % recovery of alkaloids.

FIG. 25 is a chart demonstrating a relationship between time and totalalkaloid recovery (%).

FIG. 26 is a chart demonstrating a relationship between mass of totalalkaloids applied (mg) and recovery total alkaloids (%).

FIG. 27 is a chart demonstrating a relationship between bed volumes ofeluent (BV) and recovery (%).

FIG. 28 is a chart demonstrating psilocybin content in samplePYEX-FP-200820 over 9 months at 25° C. and 65% RH

FIG. 29 is a chart demonstrating a relationship between solvent:solidratio (mL of solvent/g of dry mushroom) and % recovery of alkaloids(psilocin).

FIG. 30 is a chart demonstrating a relationship between mass of psilocinapplied (mg) and recovery of psilocin (%) from XAD4 adsorptionbreakthrough experiments.

FIG. 31 is a chart demonstrating a relationship between time (months)and recovery (%) from PIEX long-term stability measurement.

FIG. 32A is a reaction scheme of dephosphorylation of psilocybin byPsilocybe phosphatase followed by Psilocybe laccase.

FIG. 32B is a chart demonstrating a relationship between solventcomposition (v/v % solvent) and % recovery of alkaloids for the effectof aqueous extraction solvent composition.

FIG. 32C is a chart demonstrating a relationship between solventcomposition (v/v % solvent) and dry mass recovery (%) in aqueous solventcomposition.

FIG. 32D is a chart demonstrating a relationship between pH and alkaloidyield (%) for the effect of pH on alkaloid extraction yield.

FIG. 32E is a chart demonstrating a relationship between extractionsolvent concentration (methanol v/v %) and alkaloid yield (%) for theeffect of solvent composition on alkaloid yield.

DETAILED DESCRIPTION

Naturally-occurring psychoactive alkaloid comprising species haveinconsistent and often low contents of active psychoactive alkaloid(e.g., 0.1-1% dry wt). Considering fresh weight, this would mean afurther 20× reduction in content due to the large moisture content of,for example, fresh mushrooms. The content of psychoactive alkaloid innatural sources depends on various factors such as the type of source,harvesting season, and type of extraction process, to name a few. Thus,the lack of compositions having a specific desired psychoactive alkaloidcontent with no or minimal variability between different batches is amajor issue.

Maintaining physical and chemical stability is another challenge withpsychoactive alkaloid compositions. Usually a psychoactive alkaloidextract is in the form of a sticky tar, which would be difficult tohandle and formulate into standardized compositions with specifiedamounts of ingredients. Extracts are not usually amenable to processingdue to poor flowability. Extracts themselves are often not amenable todrying because many of the components that are pulled out of a plant orfungus with a lower alcohol solvent are not “dry” at room temperature(reduced sugars, oils, and waxes, for example). These same compoundseven in low concentration can cause the product to be hygroscopic andbecome clumpy, which makes encapsulation impossible, and makestabulation difficult because the powder will not “flow” in theequipment.

Thus, exposure to moisture causes psychoactive alkaloid extracts toabsorb moisture to form clumps and become susceptible to microbialgrowth. Further, the alkaloids in these extracts can degrade, usuallybecause of oxidation.

Psychoactive alkaloids present in natural sources can be broadly dividedinto two categories, which are phosphorylated psychoactive alkaloids anddephosphorylated psychoactive alkaloids, although othernon-phosphorylatable psychoactive alkaloids may also be present.

Phosphorylated psychoactive alkaloids are phosphoric acid esters ofdephosphorylated psychoactive alkaloids. For example, psilocybin is aphosphoric acid ester of psilocin, at the 4th position. Phosphorylatedpsychoactive alkaloids are biosynthesized in natural sources.Dephosphorylated psychoactive alkaloids are the bioactive forms that areconverted from phosphorylated alkaloids, through phosphatase action orchemical hydrolysis, and released when the natural source is damaged,harvested, or eaten. Because of this phenomenon, phosphorylatedpsychoactive alkaloids are often either partially or entirely convertedto dephosphorylated psychoactive alkaloids during the alkaloidextraction process, which involves harvesting as a necessary prior step.

Although the dephosphorylated psychoactive alkaloids are the bioactiveform of their counterpart phosphorylated psychoactive alkaloids,dephosphorylated psychoactive alkaloids are easily degraded intonon-bioactive compounds in the presence of light, heat, and oxygen. Forexample, oxidation of psilocin, the dephosphorylated counterpart topsilocybin, a phosphorylated alkaloid produced by biological synthesisin mushrooms, begins rapidly when exposed to air, especially insolution, and heat increases the oxidation rate. From our own data, theoxidation of psilocin in a moist and/or high light environment beginsimmediately, leading to about 10% decay within 30 minutes, 25% after 5hours, and 40-60% at 20 hours when shielded from light. Due to thisinstability of the dephosphorylated psychoactive alkaloids, thebioactivity of the psychoactive alkaloid extracts may also be unstableover time.

Extracts or compositions with an active ingredient made from naturalsources generally have increased consumer acceptance and lower cost ofproduction compared to synthetic compositions. There may be potentialbenefits of multiple natural compounds working synergistically,colloquially known as the “entourage” or “halo” effect. However, theavailability of psychoactive alkaloid compositions with a desiredspecific psychoactive alkaloid content is a major challenge faced byresearchers. The variability in the content of the psychoactivealkaloids extracted from their natural sources is a hurdle in trying toavoid variability in the psychoactive alkaloid concentration inextracted compositions. It is even more challenging to produceconsistent formulations when the concentration of active ingredientsbeing extracted is typically very low in the natural source. Maintainingphysical and chemical stability is also an issue with thesecompositions. Extracts or compositions containing psychoactive alkaloidsare often not amenable to drying, processing (due to poor flowability),or packaging methods such as tabulation or encapsulation.

This application relates to the extraction of active ingredients fromfungus and processes of purifying them. More specifically, it relates toextracting psychoactive compounds from fungus and forming an extract ofspecific purities appropriate for uses of the psychoactive compounds intherapeutic formulations. More specifically, the present inventionrelates to a purification process for obtaining a purified psychoactivealkaloid solution from an extract. Further, the present invention alsorelates to a process of forming a standardized extract from the purifiedpsychoactive alkaloid solution, wherein the extract has a desired,specific concentration of psychoactive alkaloids.

This application relates to a process of obtaining psychoactive alkaloidextracts. More specifically, the present invention relates tocontrolling dephosphorylation during extraction. Further, the presentinvention relates to psychoactive alkaloid compositions with controlleddephosphorylation.

This application relates to a composition. Particularly, thisapplication relates to psychoactive alkaloid compositions comprising anatural extract.

A. Glossary

To facilitate the understanding of this invention, a number of terms aredefined below. Terms used herein have meanings as commonly understood bya person of ordinary skill in the areas relevant to the presentinvention, unless otherwise defined. Terms such as “a”, “an” and “the”are not intended to refer to only a singular entity but include thegeneral class of which a specific example may be used for illustration.The terminology herein is used to describe specific embodiments of theinvention, but its usage does not delimit the invention, except asoutlined in the claims.

Psilocybin fungi or psilocybin mushrooms—these are a group of fungi thatcontain at least one psychoactive alkaloid, and generally containpsilocybin and psilocin. They may also contain other psychoactivealkaloids such as baeocystin, norbaeocystin, ibotenic acid andnorpsilocin. The genera of these mushrooms include Copelandia,Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, Amanita, andPsilocybe.

Psilocybe mushrooms—these form a genus of gilled mushrooms in the familyHymenogastraceae. Most species contain the psychedelic alkaloidspsilocybin, psilocin, and baeocystin.

Psilocybin—this is a psychedelic prodrug produced by numerous species ofmushrooms, collectively known as psilocybin mushrooms. Psilocybin isconverted by the body to psilocin, which has mind-altering effects suchas euphoria and hallucinations, but can also lead to nausea and panicattacks.

The term “psychoactive alkaloid extract” or “extract” refers to apsychoactive alkaloid extract that is obtained after a psychoactivealkaloid source has been extracted according to a process describedherein. The extract may be a fluid, as either a liquid or a slurry, oris made into a fluid by the addition of a solvent. The term “extract”may also be used for the dried form of the fluid extract.

The term “psychoactive alkaloid extract” used herein refers to apsychoactive alkaloid extract obtained by an extraction process of thepresent invention. The extract can be in a solid, solid-powdered,semi-solid or a slurry form.

The term “psychoactive alkaloid” as used herein refers to alkaloids thatupon ingestion are capable of changing brain function, resulting inalterations in perception, mood, consciousness, cognition, or behavior,for example. Psychoactive alkaloids are abundant in nature and can beobtained from sources such as a fungus, an animal, a mycelium, a spore,a plant, a bacterium, or a yeast. Examples of psychoactive alkaloidsinclude, but are not limited to, psilocybin, psilocin, baeocystin,norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine,5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), N,N-dimethyltryptamine(DMT), ergine (LSA), ergonovine, ergometrine, ibotenic acid, muscimol,lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine,and/or chanoclavine. The source of the psychoactive alkaloid can also bean extract or a solution comprising a psychoactive alkaloid.

The term “psychoactive alkaloid” used herein refers to alkaloids thatupon introduction to the human body are capable of changing brainfunction, for example resulting in alterations in perception, mood,consciousness, cognition, or behavior. The psychoactive alkaloid towhich the present invention applies is either a phosphorylatedpsychoactive alkaloid or a dephosphorylated psychoactive alkaloid, andthere may be multiple different compounds in each.

The term “psychoactive alkaloid source” used herein refers to a fungus,a mycelium, a spore, a plant, a bacterium, a Protista, an animal or ayeast, which has in it a phosphorylated psychoactive alkaloid, adephosphorylated psychoactive alkaloid, or a combination or both. Thesource of the psychoactive alkaloid can also be another extract or asolution with a phosphorylated psychoactive alkaloid, a dephosphorylatedpsychoactive alkaloid, or a combination of both.

The term “phosphorylatable psychoactive alkaloid” refers to psychoactivealkaloids that have phosphorylated derivatives and includes psychoactivealkaloids in both their phosphorylated and dephosphorylated forms.

The term “psychoactive alkaloid composition” used herein can also bereferred to as “composition” and describes a mixture of psychoactivealkaloid and one or more excipients. The composition can be ofpharmaceutical, nutraceutical, or veterinarian grade.

The term “psychoactive alkaloid liquid” used herein refers topsychoactive alkaloid obtained in liquid form after a dried powderedbiomass of a psychoactive alkaloid source has been extracted using anacidified solvent or a basified solvent. The liquid form can be asolution or a slurry.

The term “purified psychoactive alkaloid extract” refers to a purifiedextract that is obtained after a psychoactive alkaloid extract istreated with one or more resins for purification as described herein, orby other means of purifying the concentration of the psychoactivealkaloid concentration. This purified psychoactive alkaloid extract issubstantially free of impurities, or contains fewer impurities comparedto a similar psychoactive alkaloid extract that has not undergone anypurification. The purified psychoactive alkaloid extract is a fluid,either a liquid or a slurry, or is made into a fluid by the addition ofa solvent.

The term “purified psychoactive alkaloid solution” refers to a solutionof one or more desired psychoactive alkaloids, where the solution isfree of impurities or contains fewer impurities compared to a similarpsychoactive alkaloid solution that has not undergone any purification.The purified solution is obtained after a psychoactive alkaloidextracted from its source has been purified by the purification processof the present invention. The impurities that are commonly encounteredwhile extracting psychoactive alkaloids from a natural source includesugars, carbohydrates, chitin, chitosan, fats, minerals, waxes, and/orproteins. The impurities being removed from the psychoactive alkaloidextract will vary depending on the source of the psychoactive alkaloid.

The “impurities” herein are commonly undesired, but not necessarilyharmful, substances encountered while extracting psychoactive alkaloidsfrom psychoactive organisms. Impurities may include sugars,carbohydrates, chitin, chitosan, fats, minerals, waxes, and/or proteins.The impurities being removed from a psychoactive alkaloid extract willvary depending on the source of the psychoactive alkaloid. Their removalincreases the concentration of the desired psychoactive alkaloidsremaining in the extract.

The term “standardized psychoactive alkaloid extract” is used herein todescribe a formulation derived from the purified psychoactive alkaloidsolution, which has been standardized using a process described herein.The standardized psychoactive alkaloid extract includes psychoactivealkaloids in a specific concentration.

The term “resin” as used herein is intended to refer to a solid orhighly-viscous substance of plant, mineral, or synthetic origin that hasbeen typically converted into a polymer. Resins are usually mixtures oforganic compounds. They are typically used in chromatographic techniquesas a stationary phase to purify and separate compounds depending ontheir polarity. Resins can be physically or chemically modified toprovide specificity to bind or repel particular molecules withinsometimes very complex mixtures. A resin is an example of an adsorbentmaterial.

As used herein, the term “ion exchange resin” refers to an insolubleorganic polymer containing charged groups that tract and hold oppositelycharged ions present in a surrounding solution in exchange forcounterions previously held. Suitable ion exchange resins to be usedherein contain cationic groups that tract and hold anions present in asurrounding solution and are sometimes referred to as “anionion-exchange resins”. Similarly, other ion exchange resins to be usedherein contain anionic groups that tract and hold cations present in asurrounding solution and are sometimes referred to as “cationion-exchange resins”.

The term “macroporous resin” as used herein refers to a nonionic,cation, or anion resin with very small, highly cross-linked polymerparticles with tiny channels. Macroporous resins are generally used forthe adsorption of organic constituents due to their hydrophobicproperties and are thus used to separate and purify compounds. Theadsorption capacity of macroporous resins not only correlates with thephysical and chemical properties of the adsorbent, but also with thesize and chemical features of the adsorbed substance.

The term “adsorbed psychoactive alkaloid” refers to one or morealkaloids that are adsorbed onto an adsorbent material such as a resin.

The term “other adsorbent material” as used herein refers to materialswhich can be used in place of the resin(s) to adsorb the psychoactivealkaloids. Examples of such materials include, but are not limited to,zeolites, clays, bentonite, minerals, alumina, diatomaceous earth,activated carbon, charred biomass, and others.

The term “purification process” may be used herein to refer to theprocess described herein, i.e. a process for obtaining a purifiedpsychoactive alkaloid solution. The purification process is a separateprocess to the standardization process.

The term “standardization” when used herein refers to a process forobtaining a standardized psychoactive alkaloid composition, i.e., acomposition with a defined concentration by weight of psychoactivealkaloid.

The term “standardization process” as used herein refers to the processof obtaining a psychoactive alkaloid extract that has a definedpercentage content of psychoactive alkaloids. The standardizationprocess may be applied to an extract that has gone through apurification process or to an extract that has not gone through apurification process.

As used herein, the expression “standardizing” the psychoactive alkaloidslurry or bulk psychoactive alkaloid extract slurry refers to adding anexcipient to an extract to obtain a slurry with a specific, totalconcentration of alkaloid, by weight. The slurry may then be dried toform a powdered composition with a pre-calculated percentageconcentration by weight of psychoactive alkaloid. The total amount ofalkaloid content can be specified to an accuracy of up to threesignificant figures.

The term “psychoactive alkaloid composition” or “composition” or“standardized composition” or “standardized purified composition” isused herein to describe a composition including a psychoactive alkaloidextract or a purified psychoactive alkaloid extract, which has beenstandardized by the addition of excipients according to a presentlydescribed process. The standardized psychoactive alkaloid compositionincludes the psychoactive alkaloid in a specific amount.

As used herein, the term “specific amount” when referring to apsychoactive alkaloid content means a desired percentage, accurate toone or two decimal places or one or two significant figures, of thepsychoactive alkaloid content in a psychoactive alkaloid composition.The specific amount is defined as a percentage by weight and can beselected by a person of skill in the art according to preference.

The term “excipient” means any component added to an active ingredientto make a composition. An excipient is inert in relation to the activeingredient, in that it essentially does not act in the same way as theactive ingredient. An excipient may be completely inert, or it may havesome other property that protects the integrity of the active ingredientor assists its uptake into the human body. There are multiple types ofexcipient, each having a different purpose, and a given excipient mayfulfill more than one purpose. Examples of types of excipient includeflowability agents, flavorants, colorants, palatants, antioxidants,bioavailability-increasing agents, viscosity modifying agents, tonicityagents, drug carriers, sustained-release agents, comfort-enhancingagents, emulsifiers, solubilizing aids, lubricants, binding agents andstabilizing agents. Specific excipients include pectin, rice husks,rice, xanthum gum, gum arabic, beta cyclodextrin, alpha cyclodextrin,microcrystalline cellulose, sorbitol, dextrose, guar gum, acacia gum,cellulose gum, talc, magnesium stearate.

The phrase “one or more excipients” is used herein to refer that oneexcipient or more than one excipient can be used in any combination. Thenumber of excipients to be used will be at the discretion of a personskilled in the art, and they may be of different types.

The term “carrier” means an excipient that aids in delivery of theactive ingredient or provides bulk to the composition. The amount ofcarrier included in a composition can vary widely in order to controlthe concentration of the active ingredient in the composition. Anexample of a carrier is mannitol, starch, maltodextrin, tapiocamaltodextrin or rice maltodextrin, alpha and beta cyclodextrin,microcrystalline cellulose (MCC), gum arabic, xanthum gum, guar gum, orcellulose gum. In some embodiments, the starch is potato starch, cornstarch, tapioca starch, arrowroot starch, wheat starch, rice starch,sweet potato starch, sago starch, rung bean starch, and any combinationof thereof. In some embodiments, mannitol is a cryoprotectant (allowingfor efficient freeze-drying) and bulking agent.

The term “flow agent”, “flowability agent” or “anti-caking agent” or“anti-adherent” means an excipient that prevents or reduces theformation of lumps in a powdered composition. An example of a flow agentis silicon dioxide, stearic acid, magnesium stearate, or talc.

The term “preservative” means an excipient that is added to thecomposition to prevent microbial growth or microbial degradation of thecomposition. Examples of preservative are ascorbic acid, citric acid,lactose, vitamin A, vitamin E, retinyl palmitate, selenium, sodiumcitrate, sodium ascorbate, calcium ascorbate, sodium benzoate, andpotassium benzoate.

The term “purified water” includes deionized water, distilled water,reverse osmosis water, or otherwise purified water which issubstantially without free ions.

The term “substantially” as used herein refers to a majority of, ormostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%,98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more.

The term “specific pH” herein refers to a desired pH value of a solventor a psychoactive alkaloid liquid obtained by adding an acidifiedsolvent or a basified solvent.

The term “specific pH psychoactive alkaloid solution” used herein refersto a solution that is obtained after addition of a suitable acid or abase to a psychoactive alkaloid extract to achieve a solution with adesired pH level.

The term “% wt” is used to describe the weight percentage of onecomponent in a mixture of components.

The term “a trace” herein refers more than, but close to about 0%.

The term “about” herein refers to ±10%, ±20%, ±30%, ±40%, or ±50%, or tothe nearest significant figure.

The term “specific ratio” herein refers to a weight ratio between aphosphorylated psychoactive alkaloid and a dephosphorylated psychoactivealkaloid present in a psychoactive alkaloid composition. The ratio canbe altered by a person of skill in the art according to preference.

The term “desired amount” herein refers to an amount of a phosphorylatedpsychoactive alkaloid or a dephosphorylated psychoactive alkaloid in atotal phosphorylatable psychoactive alkaloid content, in thepsychoactive alkaloid liquid, extract or composition. The amount of eachof these alkaloids is controlled by the process for making thepsychoactive alkaloid extract or psychoactive alkaloid composition. Theamount can be altered by a person of skill in the art according topreference. The amount is usually a percentage ratio by weight that maybe accurate up to two significant figures.

The term “therapeutic effects” is intended to qualify the amount ofactive ingredients required in the treatment of a disease or disorder oron the effecting of a clinical endpoint. Reference to “treatment” of apatient is intended to include prophylaxis. Treatment may also bepreemptive in nature, i.e., it may include prevention of disease.Prevention of a disease may involve complete protection from disease,for example as in the case of prevention of infection with a pathogen ormay involve prevention of disease progression. For example, preventionof a disease may not mean complete foreclosure of any effect related tothe diseases at any level, but instead may mean prevention of thesymptoms of a disease to a clinically significant or detectable level.Prevention of diseases may also mean prevention of progression of adisease to a later stage of the disease.

In some embodiments, as the ranges become narrower and more centralcompared to the greatest range, the properties of the embodimentsgenerally become more balanced, such properties being solubility,viscosity, flowability, stability, taste, potency, immediate potency,delayed potency, cost of production, efficiency of production,production time, compatibility of the psychoactive alkaloid composition,psychoactive efficacy of the psychoactive alkaloid extract, psychoactiveefficacy of the psychoactive alkaloid composition, and so on. As theranges become narrower towards one extreme or other of the widest range,a particular property of the composition or process becomes morepronounced relative to the other properties. The specific range is to bechosen depending on how the properties are to be traded-off against eachother.

Throughout the description, specific details have been set forth inorder to provide a more thorough understanding of the invention.However, the invention may be practiced without these particulars. Inother instances, well-known elements have not been shown or described indetail and repetitions of steps and features have been omitted to avoidunnecessarily obscuring the invention. Accordingly, the specificationand drawings are to be regarded in an illustrative, rather than arestrictive, sense.

It will be clear to one having skill in the art that further variationsto the specific details disclosed herein can be made, resulting in otherembodiments that are within the scope of the invention disclosed. Stepsin the flowchart may be performed in a different order, other steps maybe added, or one or more may be removed without altering the mainoutcome of the process.

B. Compositions

Source of Psychoactive Alkaloid Extract

In one embodiment, the psychoactive alkaloid source is a psychoactiveorganism. In one embodiment, the psychoactive organism is a fungus. Inone embodiment, the fungus is a mushroom from the genus Conocybe,Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina,Pluteus or Psilocybe, or any combination of mushrooms selectedtherefrom. In one embodiment, gills, caps, stems, or the whole of thefungi is used as the alkaloid source.

The psychoactive organism may be a fungus, a mycelium, an animal, aspore, a plant, a bacterium, a protista, or a yeast. The psychoactivealkaloid source in some embodiments may be a prior extract of one ormore psychoactive alkaloids, where the prior extract is to undergo afurther extraction process. The psychoactive alkaloid may include, butis not limited to, psilocybin, psilocin, baeocystin, norbaeocystin,norpsilocin, aeruginascin, bufotenin, bufotenidine,5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), N,N-dimethyltryptamine(DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid,lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine,and/or chanoclavine, or any combination selected therefrom. It ispossible that other psychoactive alkaloids, not yet discovered, may alsobe extracted using the methods disclosed herein.

In some embodiments, the psychoactive alkaloid is a combination ofpsilocybin and psilocin. In another embodiment, the psychoactivealkaloid is psilocybin. In yet another embodiment, the psychoactivealkaloid is psilocin.

Although the examples of the present invention have been formulatedspecifically using Psilocybe cubensis and Anadenanthera peregrina assources to obtain a psychoactive alkaloid extract, the extract includingpsilocybin and psilocin in the first case and bufotenin, bufotenidine,and 5-MeO-DMT in the second, other sources are also possible. A personskilled in the art would appreciate that Psilocybe cubensis andAnadenanthera peregrina can be readily substituted by other sources ofpsychoactive alkaloids to obtain a variety of purified psychoactivealkaloids having similar properties, such alkaloids being, besides thosementioned above, baeocystin, norbaeocystin, norpsilocin, aeruginascin,N,N-dimethyltryptamine (DMT), ergine (LSA), ibotenic acid, ergonovine,ergometrine, muscimol, lysergic acid hydroxyethylamide (LSH),elymoclavine, ergometrinine, and/or chanoclavine, to name a few, and toresult in compositions with similar efficacy and efficiency as well. Forexample, the venom of the toad Incilius alvarius, the Anandenantheracolubrina tree or the Amanita muscaria mushroom may be used as othersources of psychoactive alkaloids. Note that the lists of sources andpsychoactive alkaloids are included to provide examples and arenon-exhaustive lists.

Psychoactive Ingredient

In some embodiments, the present disclosure comprises a compositionhaving, by weight, 2-99.7% of a psychoactive alkaloid extract, and0.3-98%, i.e., the remainder, being one or more excipients. In someembodiments, the psychoactive ingredient is present in the compositionat, by weight, about 50% to about 99.7%. In some embodiments, thepsychoactive ingredient is present in the composition at, by weight,about 50% to about 60%, about 50% to about 70%, about 50% to about 80%,about 50% to about 90%, about 50% to about 92%, about 50% to about 94%,about 50% to about 96%, about 50% to about 98%, about 50% to about 99%,about 50% to about 99.7%, about 60% to about 70%, about 60% to about80%, about 60% to about 90%, about 60% to about 92%, about 60% to about94%, about 60% to about 96%, about 60% to about 98%, about 60% to about99%, about 60% to about 99.7%, about 70% to about 80%, about 70% toabout 90%, about 70% to about 92%, about 70% to about 94%, about 70% toabout 96%, about 70% to about 98%, about 70% to about 99%, about 70% toabout 99.7%, about 80% to about 90%, about 80% to about 92%, about 80%to about 94%, about 80% to about 96%, about 80% to about 98%, about 80%to about 99%, about 80% to about 99.7%, about 90% to about 92%, about90% to about 94%, about 90% to about 96%, about 90% to about 98%, about90% to about 99%, about 90% to about 99.7%, about 92% to about 94%,about 92% to about 96%, about 92% to about 98%, about 92% to about 99%,about 92% to about 99.7%, about 94% to about 96%, about 94% to about98%, about 94% to about 99%, about 94% to about 99.7%, about 96% toabout 98%, about 96% to about 99%, about 96% to about 99.7%, about 98%to about 99%, about 98% to about 99.7%, or about 99% to about 99.7%. Insome embodiments, the psychoactive ingredient is present in thecomposition at, by weight, about 50%, about 60%, about 70%, about 80%,about 90%, about 92%, about 94%, about 96%, about 98%, about 99%, orabout 99.7%. In some embodiments, the psychoactive ingredient is presentin the composition at, by weight, at least about 50%, about 60%, about70%, about 80%, about 90%, about 92%, about 94%, about 96%, about 98%,or about 99%. In some embodiments, the psychoactive ingredient ispresent in the composition at, by weight, at most about 60%, about 70%,about 80%, about 90%, about 92%, about 94%, about 96%, about 98%, about99%, or about 99.7%.

While a broad range of psychoactive extract is possible, if it is above90% (e.g., as much as 99.9%), it is likely not to be dryable and/orflowable. Nevertheless, such a composition, when standardized, may stillhave its uses, due to the reliability and repeatability of thepsychoactive alkaloid content. Below about 2%, the composition may beconsidered to provide too low a dose of psychoactive alkaloid. However,compositions with less than 2% (e.g., down to 0.1%) may be possible ifmicro-dosing is desired. In some embodiments, the psychoactiveingredient is present in the composition at, by weight, about 0.05% toabout 5%. In some embodiments, the psychoactive ingredient is present inthe composition at, by weight, about 5% to about 4%, about 5% to about3%, about 5% to about 2%, about 5% to about 1%, about 5% to about 0.8%,about 5% to about 0.6%, about 5% to about 0.4%, about 5% to about 0.2%,about 5% to about 0.1%, about 5% to about 0.05%, about 4% to about 3%,about 4% to about 2%, about 4% to about 1%, about 4% to about 0.8%,about 4% to about 0.6%, about 4% to about 0.4%, about 4% to about 0.2%,about 4% to about 0.1%, about 4% to about 0.05%, about 3% to about 2%,about 3% to about 1%, about 3% to about 0.8%, about 3% to about 0.6%,about 3% to about 0.4%, about 3% to about 0.2%, about 3% to about 0.1%,about 3% to about 0.05%, about 2% to about 1%, about 2% to about 0.8%,about 2% to about 0.6%, about 2% to about 0.4%, about 2% to about 0.2%,about 2% to about 0.1%, about 2% to about 0.05%, about 1% to about 0.8%,about 1% to about 0.6%, about 1% to about 0.4%, about 1% to about 0.2%,about 1% to about 0.1%, about 1% to about 0.05%, about 0.8% to about0.6%, about 0.8% to about 0.4%, about 0.8% to about 0.2%, about 0.8% toabout 0.1%, about 0.8% to about 0.05%, about 0.6% to about 0.4%, about0.6% to about 0.2%, about 0.6% to about 0.1%, about 0.6% to about 0.05%,about 0.4% to about 0.2%, about 0.4% to about 0.1%, about 0.4% to about0.05%, about 0.2% to about 0.1%, about 0.2% to about 0.05%, or about0.1% to about 0.05%. In some embodiments, the psychoactive ingredient ispresent in the composition at, by weight, about 5%, about 4%, about 3%,about 2%, about 1%, about 0.8%, about 0.6%, about 0.4%, about 0.2%,about 0.1%, or about 0.05%. In some embodiments, the psychoactiveingredient is present in the composition at, by weight, at least about5%, about 4%, about 3%, about 2%, about 1%, about 0.8%, about 0.6%,about 0.4%, about 0.2%, or about 0.1%. In some embodiments, thepsychoactive ingredient is present in the composition at, by weight, atmost about 4%, about 3%, about 2%, about 1%, about 0.8%, about 0.6%,about 0.4%, about 0.2%, about 0.1%, or about 0.05%.

In some embodiments, the psychoactive alkaloid extract has apsychoactive alkaloid concentration ranging from 0.1% to 99% by weightof the extract. It may be in the range of 1-10% dry wt/wt % for thenon-purified extract concentration. However, as the composition may bemade with purified extract, the psychoactive concentration could be ashigh as 99%. In some embodiments, the psychoactive alkaloid extract hasa psychoactive alkaloid concentration ranging from 1.03% to 75.22% byweight of the dry extract. In some embodiments, the psychoactivealkaloid extract has a psychoactive alkaloid concentration ranging from1.03% to 3.02% by weight of the extract. In other embodiments, thepsychoactive alkaloid extract is a purified psychoactive alkaloidextract. In some embodiments, the purified psychoactive alkaloid extracthas a psychoactive alkaloid concentration ranging from 10% to 99% byweight of the extract. In other embodiments, the purified psychoactivealkaloid extract has a psychoactive alkaloid concentration ranging from16.12% to 75.22% by weight of the extract. In some embodiments, thepsychoactive ingredient is present in the composition at, by weight,about 5% to about 76%. In some embodiments, the psychoactive ingredientis present in the composition at, by weight, about 5% to about 10%,about 5% to about 20%, about 5% to about 30%, about 5% to about 40%,about 5% to about 50%, about 5% to about 60%, about 5% to about 70%,about 5% to about 75%, about 5% to about 76%, about 10% to about 20%,about 10% to about 30%, about 10% to about 40%, about 10% to about 50%,about 10% to about 60%, about 10% to about 70%, about 10% to about 75%,about 10% to about 76%, about 20% to about 30%, about 20% to about 40%,about 20% to about 50%, about 20% to about 60%, about 20% to about 70%,about 20% to about 75%, about 20% to about 76%, about 30% to about 40%,about 30% to about 50%, about 30% to about 60%, about 30% to about 70%,about 30% to about 75%, about 30% to about 76%, about 40% to about 50%,about 40% to about 60%, about 40% to about 70%, about 40% to about 75%,about 40% to about 76%, about 50% to about 60%, about 50% to about 70%,about 50% to about 75%, about 50% to about 76%, about 60% to about 70%,about 60% to about 75%, about 60% to about 76%, about 70% to about 75%,about 70% to about 76%, or about 75% to about 76%. In some embodiments,the psychoactive ingredient is present in the composition at, by weight,about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about60%, about 70%, about 75%, or about 76%. In some embodiments, thepsychoactive ingredient is present in the composition at, by weight, atleast about 5%, about 10%, about 20%, about 30%, about 40%, about 50%,about 60%, about 70%, or about 75%. In some embodiments, thepsychoactive ingredient is present in the composition at, by weight, atmost about 10%, about 20%, about 30%, about 40%, about 50%, about 60%,about 70%, about 75%, or about 76%.

The composition of the present invention has the psychoactive alkaloidpresent in a specific amount. In some embodiments, the specific amountof psychoactive alkaloid is accurate to one significant figure. Inanother embodiment, the specific amount psychoactive alkaloid isaccurate to two, three or four significant figures. The presence of thepsychoactive alkaloid in a specific amount in the composition allows forthe same desired specific amount of the psychoactive alkaloid to bepresent in various batches of the psychoactive alkaloid composition.

The composition of the present invention is in a powder form. Thecomponents of the composition are also in powder form. The compositionof the present invention may be in the form of a free-flowing powderdepending on the embodiment. Such compositions are thus easy to handleduring manufacturing and packaging processes. Further, the dry,free-flowing powder form allows the composition to be free from clumpsand not be as susceptible to microbial growth as a composition withclumping due to moisture absorption.

Phosphorylatable Psychoactive Alkaloid

In one embodiment, the present invention also relates to a psychoactivealkaloid composition. The psychoactive alkaloid composition includes aspecific amount of a total phosphorylatable psychoactive alkaloidcontent, made up of a desired amount of a phosphorylated psychoactivealkaloid and a desired amount of a dephosphorylated psychoactivealkaloid, and one or more excipients.

In some embodiments, the phosphorylated alkaloid is psilocybin,baeocystin, norbaeocystin, aeruginascin, or any combination therefrom;and the dephosphorylated alkaloid is psilocin, norpsilocin,4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine, or anycombination therefrom. In other embodiments, the phosphorylated alkaloidis psilocybin and the dephosphorylated alkaloid is psilocin.

In some embodiments, any source that contains phosphorylatedpsychoactive alkaloids may be used as the psychoactive alkaloid source.

In one embodiment, the specific amount of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid compositionranges from 0.1-99% by weight of the composition. In another embodiment,the specific amount of the total phosphorylatable psychoactive alkaloidcontent in the psychoactive alkaloid composition ranges from 0.1-10% byweight of the composition. In an exemplary embodiment, the specificamount of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid composition is 0.533% by weight of thecomposition. In yet another exemplary embodiment, the specific amount ofthe total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid composition is 0.501% by weight of thecomposition.

In one embodiment, the desired amount of the phosphorylated psychoactivealkaloid is 0-100% by weight of a total phosphorylatable psychoactivealkaloid content in the psychoactive alkaloid extract, and the desiredamount of the dephosphorylated psychoactive alkaloid is the remainder ofthe total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid extract. In one embodiment, the desired amount ofthe phosphorylated psychoactive alkaloid is 10-90% by weight of thetotal phosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is the remainder of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Inanother embodiment, the desired amount of the phosphorylatedpsychoactive alkaloid is 0% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract, andthe desired amount of the dephosphorylated psychoactive alkaloid is 100%by weight of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract. In yet another embodiment, thedesired amount of the phosphorylated psychoactive alkaloid is 100% byweight of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract, and the desired amount of thedephosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract.

In some embodiments, a maximum desired amount of the phosphorylatedalkaloid is limited by an amount of the dephosphorylated alkaloid in thepsychoactive alkaloid source.

In an exemplary embodiment, the desired amount of the phosphorylatedpsychoactive alkaloid is 0.503% by weight of the psychoactive alkaloidcomposition; and the desired amount of the dephosphorylated psychoactivealkaloid is by 0.03% weight of the psychoactive alkaloid composition. Inyet another exemplary embodiment, the desired amount of thephosphorylated psychoactive alkaloid is 0.00% by weight of thepsychoactive alkaloid composition, and the desired amount of thedephosphorylated psychoactive alkaloid is by 0.501% weight of thepsychoactive alkaloid composition.

In one embodiment, the desired amount of the phosphorylated psychoactivealkaloid is 100% by weight of the total psychoactive alkaloid content inthe psychoactive alkaloid extract.

In one embodiment, the desired amount of the dephosphorylatedpsychoactive alkaloid is 100% by weight of the total psychoactivealkaloid content in the psychoactive alkaloid extract.

The dephosphorylated psychoactive alkaloids are quicker in becomingbioavailable than their phosphorylated psychoactive alkaloidscounterparts. Thus, the psychoactive compositions comprisingdephosphorylated psychoactive alkaloids 100% by weight in the totalphosphorylatable psychoactive alkaloid content may exhibit therapeuticeffects faster than psychoactive alkaloid compositions comprisingphosphorylated psychoactive alkaloids as the majority alkaloids in thetotal phosphorylatable psychoactive alkaloid content.

In one embodiment, the psychoactive alkaloid composition is obtained bythe process for obtaining a psychoactive alkaloid extract with a desiredamount of a phosphorylated psychoactive alkaloid and a desired amount ofa dephosphorylated psychoactive alkaloid of the present invention.

In one embodiment, the present invention also relates to a psychoactivealkaloid composition with a specific ratio of a phosphorylatedpsychoactive alkaloid and a dephosphorylated psychoactive alkaloid. Thecomposition includes a psychoactive alkaloid extract having a totalphosphorylatable psychoactive alkaloid content of 100% by weight of aphosphorylated psychoactive alkaloid, another psychoactive alkaloidextract having a total phosphorylatable psychoactive alkaloid content of100% by weight of a dephosphorylated psychoactive alkaloid, and one ormore excipients.

In some embodiments, the composition includes a psychoactive alkaloidextract having a total phosphorylated psychoactive alkaloid content of atrace by weight to about 100% by weight. In some embodiments, thecomposition includes a psychoactive alkaloid extract having a totalphosphorylated psychoactive alkaloid content of a trace by weight toabout 10% by weight, a trace by weight to about 20% by weight, a traceby weight to about 30% by weight, a trace by weight to about 40% byweight, a trace by weight to about 50% by weight, a trace by weight toabout 60% by weight, a trace by weight to about 70% by weight, a traceby weight to about 80% by weight, a trace by weight to about 90% byweight, a trace by weight to about 95% by weight, a trace by weight toabout 100% by weight, about 10% by weight to about 20% by weight, about10% by weight to about 30% by weight, about 10% by weight to about 40%by weight, about 10% by weight to about 50% by weight, about 10% byweight to about 60% by weight, about 10% by weight to about 70% byweight, about 10% by weight to about 80% by weight, about 10% by weightto about 90% by weight, about 10% by weight to about 95% by weight,about 10% by weight to about 100% by weight, about 20% by weight toabout 30% by weight, about 20% by weight to about 40% by weight, about20% by weight to about 50% by weight, about 20% by weight to about 60%by weight, about 20% by weight to about 70% by weight, about 20% byweight to about 80% by weight, about 20% by weight to about 90% byweight, about 20% by weight to about 95% by weight, about 20% by weightto about 100% by weight, about 30% by weight to about 40% by weight,about 30% by weight to about 50% by weight, about 30% by weight to about60% by weight, about 30% by weight to about 70% by weight, about 30% byweight to about 80% by weight, about 30% by weight to about 90% byweight, about 30% by weight to about 95% by weight, about 30% by weightto about 100% by weight, about 40% by weight to about 50% by weight,about 40% by weight to about 60% by weight, about 40% by weight to about70% by weight, about 40% by weight to about 80% by weight, about 40% byweight to about 90% by weight, about 40% by weight to about 95% byweight, about 40% by weight to about 100% by weight, about 50% by weightto about 60% by weight, about 50% by weight to about 70% by weight,about 50% by weight to about 80% by weight, about 50% by weight to about90% by weight, about 50% by weight to about 95% by weight, about 50% byweight to about 100% by weight, about 60% by weight to about 70% byweight, about 60% by weight to about 80% by weight, about 60% by weightto about 90% by weight, about 60% by weight to about 95% by weight,about 60% by weight to about 100% by weight, about 70% by weight toabout 80% by weight, about 70% by weight to about 90% by weight, about70% by weight to about 95% by weight, about 70% by weight to about 100%by weight, about 80% by weight to about 90% by weight, about 80% byweight to about 95% by weight, about 80% by weight to about 100% byweight, about 90% by weight to about 95% by weight, about 90% by weightto about 100% by weight, or about 95% by weight to about 100% by weight.In some embodiments, the composition includes a psychoactive alkaloidextract having a total phosphorylated psychoactive alkaloid content of atrace by weight, about 10% by weight, about 20% by weight, about 30% byweight, about 40% by weight, about 50% by weight, about 60% by weight,about 70% by weight, about 80% by weight, about 90% by weight, about 95%by weight, or about 100% by weight. In some embodiments, the compositionincludes a psychoactive alkaloid extract having a total phosphorylatedpsychoactive alkaloid content of at least a trace by weight, about 10%by weight, about 20% by weight, about 30% by weight, about 40% byweight, about 50% by weight, about 60% by weight, about 70% by weight,about 80% by weight, about 90% by weight, or about 95% by weight. Insome embodiments, the composition includes a psychoactive alkaloidextract having a total phosphorylated psychoactive alkaloid content ofat most about 10% by weight, about 20% by weight, about 30% by weight,about 40% by weight, about 50% by weight, about 60% by weight, about 70%by weight, about 80% by weight, about 90% by weight, about 95% byweight, or about 100% by weight.

In some embodiments, the composition includes a psychoactive alkaloidextract having a total dephosphorylated psychoactive alkaloid content ofa trace by weight to about 100% by weight. In some embodiments, thecomposition includes a psychoactive alkaloid extract having a totaldephosphorylated psychoactive alkaloid content of a trace by weight toabout 10% by weight, a trace by weight to about 20% by weight, a traceby weight to about 30% by weight, a trace by weight to about 40% byweight, a trace by weight to about 50% by weight, a trace by weight toabout 60% by weight, a trace by weight to about 70% by weight, a traceby weight to about 80% by weight, a trace by weight to about 90% byweight, a trace by weight to about 95% by weight, a trace by weight toabout 100% by weight, about 10% by weight to about 20% by weight, about10% by weight to about 30% by weight, about 10% by weight to about 40%by weight, about 10% by weight to about 50% by weight, about 10% byweight to about 60% by weight, about 10% by weight to about 70% byweight, about 10% by weight to about 80% by weight, about 10% by weightto about 90% by weight, about 10% by weight to about 95% by weight,about 10% by weight to about 100% by weight, about 20% by weight toabout 30% by weight, about 20% by weight to about 40% by weight, about20% by weight to about 50% by weight, about 20% by weight to about 60%by weight, about 20% by weight to about 70% by weight, about 20% byweight to about 80% by weight, about 20% by weight to about 90% byweight, about 20% by weight to about 95% by weight, about 20% by weightto about 100% by weight, about 30% by weight to about 40% by weight,about 30% by weight to about 50% by weight, about 30% by weight to about60% by weight, about 30% by weight to about 70% by weight, about 30% byweight to about 80% by weight, about 30% by weight to about 90% byweight, about 30% by weight to about 95% by weight, about 30% by weightto about 100% by weight, about 40% by weight to about 50% by weight,about 40% by weight to about 60% by weight, about 40% by weight to about70% by weight, about 40% by weight to about 80% by weight, about 40% byweight to about 90% by weight, about 40% by weight to about 95% byweight, about 40% by weight to about 100% by weight, about 50% by weightto about 60% by weight, about 50% by weight to about 70% by weight,about 50% by weight to about 80% by weight, about 50% by weight to about90% by weight, about 50% by weight to about 95% by weight, about 50% byweight to about 100% by weight, about 60% by weight to about 70% byweight, about 60% by weight to about 80% by weight, about 60% by weightto about 90% by weight, about 60% by weight to about 95% by weight,about 60% by weight to about 100% by weight, about 70% by weight toabout 80% by weight, about 70% by weight to about 90% by weight, about70% by weight to about 95% by weight, about 70% by weight to about 100%by weight, about 80% by weight to about 90% by weight, about 80% byweight to about 95% by weight, about 80% by weight to about 100% byweight, about 90% by weight to about 95% by weight, about 90% by weightto about 100% by weight, or about 95% by weight to about 100% by weight.In some embodiments, the composition includes a psychoactive alkaloidextract having a total dephosphorylated psychoactive alkaloid content ofa trace by weight, about 10% by weight, about 20% by weight, about 30%by weight, about 40% by weight, about 50% by weight, about 60% byweight, about 70% by weight, about 80% by weight, about 90% by weight,about 95% by weight, or about 100% by weight. In some embodiments, thecomposition includes a psychoactive alkaloid extract having a totaldephosphorylated psychoactive alkaloid content of at least a trace byweight, about 10% by weight, about 20% by weight, about 30% by weight,about 40% by weight, about 50% by weight, about 60% by weight, about 70%by weight, about 80% by weight, about 90% by weight, or about 95% byweight. In some embodiments, the composition includes a psychoactivealkaloid extract having a total dephosphorylated psychoactive alkaloidcontent of at most about 10% by weight, about 20% by weight, about 30%by weight, about 40% by weight, about 50% by weight, about 60% byweight, about 70% by weight, about 80% by weight, about 90% by weight,about 95% by weight, or about 100% by weight.

In one embodiment, one psychoactive alkaloid extract and anotherpsychoactive alkaloid extract are present in a proportion such that thespecific ratio of phosphorylated to dephosphorylated psychoactivealkaloid ranges from 1:1000 to 1000:1. In exemplary embodiments, aphosphorylated psychoactive alkaloid extract and a dephosphorylatedpsychoactive alkaloid extract are present in a proportion such that thespecific ratio of phosphorylated to dephosphorylated psychoactivealkaloid is 1:1, 1:3, and 3:1.

In other embodiments, the psychoactive alkaloid composition is definedby a specific total amount of psychoactive alkaloid content, which has aknown ratio of phosphorylated and dephosphorylated alkaloids.

In some embodiments, the psychoactive alkaloid composition with aspecific ratio of a phosphorylated psychoactive alkaloid and adephosphorylated psychoactive alkaloid is made by the process forobtaining a psychoactive alkaloid composition with a specific ratio of aphosphorylated psychoactive alkaloid to a dephosphorylated psychoactivealkaloid of the present invention.

The psychoactive alkaloid extract of the composition low in (e.g., <20%)or almost free of undesired impurities allows a smaller amount of thecomposition to achieve a desired therapeutic effect than if the extractwere less concentrated, with more impurities.

The psychoactive alkaloid composition of the present invention is inpowder form. This free-flowing powder form allows the composition to beeasily handled. The components of the composition are also in powderform.

The psychoactive alkaloid composition of the present invention can beused, for example, in medical research on the use of psychedelicsubstances in treatments for mental illnesses.

FIG. 22 , in another embodiment, describes a process for preparing apsychoactive alkaloid composition having a phosphorylated psychoactivealkaloid from one psychoactive alkaloid extraction and adephosphorylated psychoactive alkaloid from another psychoactivealkaloid extraction in a specific ratio.

A dried powdered biomass is obtained in step 2201. Step 2202 includesextracting a psychoactive alkaloid with a basified solvent to obtain apsychoactive alkaloid liquid with a pH greater than 10.5. A majority, orall, of a total phosphorylatable psychoactive alkaloid content isphosphorylated alkaloid and a remainder thereof is dephosphorylatedalkaloid.

In step 2203 the pH of the resulting psychoactive alkaloid liquid isadjusted to a pH ranging from 3.5 to 4.5. The pH is adjusted by addingan acid.

Another dried powdered biomass is obtained in step 2206. Step 2207includes extracting a psychoactive alkaloid with an acidified solvent toobtain another psychoactive alkaloid liquid with a pH lower than 3.5.All of the psychoactive alkaloid present is dephosphorylated.

Step 2208 involves adjusting the pH of the second psychoactive alkaloidliquid to a pH ranging from 3.5 to 4.5. The pH is adjusted by adding abase.

In steps 2204 and 2209, a portion of the basified solvent from the firstpsychoactive alkaloid liquid and a portion of the acidified solvent fromthe second psychoactive alkaloid liquid are evaporated to obtain firstand second psychoactive alkaloid slurries 2205 and 2210 respectively.

In step 2211, measured portions of the psychoactive alkaloid slurriesare mixed to obtain a bulk psychoactive alkaloid slurry. The bulkpsychoactive alkaloid slurry includes the phosphorylated psychoactivealkaloid and the dephosphorylated psychoactive alkaloid in the specificratio. The measured portions, by weight, of each of the psychoactivealkaloid slurries are chosen in such a manner as to achieve the specificratio of the phosphorylated psychoactive alkaloid and thedephosphorylated psychoactive alkaloid, taking into account thepercentage by weight of these psychoactive alkaloids in each of theinitial slurries. In one exemplary embodiment, mixing 100 g of a 1.0%phosphorylated psychoactive alkaloid slurry, with 50 g of a 0.5%dephosphorylated psychoactive alkaloid slurry results in the specificratio of 4:1 of phosphorylated to dephosphorylated alkaloid.

In step 2212, the obtained bulk psychoactive alkaloid slurry isstandardized by adding thereto a measured quantity of one or moreexcipients to obtain a standardized bulk slurry with a specific totalamount of psychoactive alkaloid.

Step 2213 includes drying the standardized bulk psychoactive alkaloidslurry by evaporation to obtain the psychoactive alkaloid composition.The obtained psychoactive alkaloid composition has a specific totalamount of psychoactive alkaloid content, and the phosphorylatedpsychoactive alkaloid and dephosphorylated psychoactive alkaloid are inthe specific ratio. In some embodiments of the psychoactive alkaloidcomposition, the specific ratio of phosphorylated psychoactive alkaloidto dephosphorylated psychoactive alkaloid ranges from 1:1000 to 1000:1.

Mixture

Referring to FIG. 21 , in one embodiment, the present invention alsorelates to a process for preparing a psychoactive alkaloid compositionby mixing a phosphorylated psychoactive alkaloid composition and adephosphorylated psychoactive alkaloid composition in a specific ratio.In step 2100, the psychoactive alkaloid composition obtained after step2020 (FIG. 20 ) is taken. The psychoactive alkaloid composition in step2020 has the desired amount of the dephosphorylated psychoactivealkaloid of 100% by weight of the total phosphorylatable psychoactivealkaloid content in the psychoactive alkaloid extract. The aforesaid isachieved by extracting the psychoactive alkaloid from the dried powderedbiomass with an acidified solvent having a specific pH lower than 3.5.

In step 2110, another psychoactive alkaloid composition is obtainedaccording to the process described above. This other psychoactivealkaloid composition has a desired amount of phosphorylated psychoactivealkaloid of 100% by weight of the total phosphorylatable psychoactivealkaloid content. The aforesaid is achieved by extracting thepsychoactive alkaloid from the dried powdered biomass with a basifiedsolvent having a pH greater than 10.5, where the biomass is notdephosphorylated or not significantly dephosphorylated.

In some embodiments, the acidified solvent is a mixture of an acid and aC1-C4 primary aliphatic alcohol, a C3-C4 ketone, water, or anycombination selected therefrom. The acid may be citric acid, ascorbicacid, formic acid, acetic acid, hydrochloric acid, phosphoric acid,sulfuric acid, or any combination selected therefrom. In otherembodiments, the basified solvent is a mixture of a base and a C1-C4primary aliphatic alcohol, a C3-C4 ketone, water, or any combinationselected therefrom. The base may be sodium hydroxide, potassiumhydroxide, ammonium hydroxide, sodium bicarbonate, calcium carbonate, orany combination selected therefrom.

In step 2120, both psychoactive alkaloid compositions are mixed in ameasured ratio to obtain a psychoactive alkaloid composition. Thiscomposition includes the dephosphorylated psychoactive alkaloid of thefirst psychoactive alkaloid composition and the phosphorylatedpsychoactive alkaloid of the second psychoactive alkaloid composition ina specific ratio. In some embodiments, the specific ratio ofphosphorylated psychoactive alkaloid to dephosphorylated psychoactivealkaloid is in the range from 1000:1 to 1:1000. If the totalphosphorylatable psychoactive alkaloid concentrations are the same inboth starting compositions, then the final ratio of phosphorylated todephosphorylated alkaloids is the same as the ratio in which thestarting compositions are mixed. However, in other embodiments, themixing ratio may need to be modified to take into account the differentstarting concentrations of the phosphorylated and dephosphorylatedalkaloids in their respective compositions. In yet other embodiments,one of the starting compositions may include both phosphorylated anddephosphorylated alkaloids, and the mixing ratio of the two compositionsmay be adjusted to take this into account.

Naturally Occurring Substances

In other embodiments, the psychoactive alkaloid extract includesnaturally occurring substances selected from fats, sugars,carbohydrates, and proteins, or any combination selected therefrom. Theaforesaid naturally occurring substances do not lead to any side effectsor adverse effects when ingested as a part of the composition.

The naturally-occurring substances are present in the psychoactivealkaloid extract in a concentration ranging from 1-99.9% by dry weight.The concentration range of the naturally-occurring substances in thepsychoactive alkaloid extract will vary due to various factors forexample, but not limited to, the source of the psychoactive alkaloidextract, the extraction technique used, the efficiency of the extractionprocess, and the amount of the psychoactive alkaloid in the extract.

In some embodiments, the psychoactive alkaloid extract includes thepsychoactive alkaloid and the naturally occurring substances.

Excipient

The excipients described herein refer to excipients which aid in themanufacturing and/or administration of the compositions describedherein. Non-limiting examples of such excipients are well known in theart and include flavorants, colorants, palatants, antioxidants,viscosity modifying agents, tonicity agents, drug carriers,sustained-release agents, comfort-enhancing agents, emulsifiers,solubilizing aids, lubricants, binding agents, stabilizing agents andother agents to aid in the manufacturing and/or administration of thecompositions. The excipients used in the present invention areacceptable for use in pharmaceutical or nutraceutical applications or asfood ingredients. The amount of excipients will vary depending on theconcentration of psychoactive alkaloids in the psychoactive alkaloidextract to result in a flowable psychoactive alkaloid composition, whichwill be obvious to a person of skill in the art.

In some embodiments, a bioavailability enhancing agent such as citricacid, beta cyclodextrin, or alpha cyclodextrin can be added (up to 0.5%by weight) as an excipient. In other embodiments, an antioxidant agentsuch as ascorbic acid may be added (up to 0.5% by weight) as anexcipient.

In some embodiments, the excipients are selected from silicon dioxide,ascorbic acid, maltodextrin from corn, potato, or tapioca for example,gum arabic, microcrystalline cellulose, sodium benzoate, sodiumphosphate, sodium citrate, rice hulls, and rice. A combination of any ofthese excipients may be used.

In some embodiments, the carrier comprises maltodextrin in thecomposition at 10% to 20%. In some embodiments, the carrier comprisesmaltodextrin in the composition at about 10% to about 12%, about 10% toabout 14%, about 10% to about 16%, about 10% to about 18%, about 10% toabout 20%, about 12% to about 14%, about 12% to about 16%, about 12% toabout 18%, about 12% to about 20%, about 14% to about 16%, about 14% toabout 18%, about 14% to about 20%, about 16% to about 18%, about 16% toabout 20%, or about 18% to about 20%. In some embodiments, the carriercomprises maltodextrin in the composition at about 10%, about 12%, about14%, about 16%, about 18%, or about 20%. In some embodiments, thecarrier comprises maltodextrin in the composition at least about 10%,about 12%, about 14%, about 16%, or about 18%. In some embodiments, thecarrier comprises maltodextrin in the composition at most about 12%,about 14%, about 16%, about 18%, or about 20%.

In some embodiments, the carrier comprises mannitol in the compositionat 10% to 20%. In some embodiments, the carrier comprises mannitol inthe composition at about 10% to about 12%, about 10% to about 14%, about10% to about 16%, about 10% to about 18%, about 10% to about 20%, about12% to about 14%, about 12% to about 16%, about 12% to about 18%, about12% to about 20%, about 14% to about 16%, about 14% to about 18%, about14% to about 20%, about 16% to about 18%, about 16% to about 20%, orabout 18% to about 20%. In some embodiments, the carrier comprisesmannitol in the composition at about 10%, about 12%, about 14%, about16%, about 18%, or about 20%. In some embodiments, the carrier comprisesmannitol in the composition at least about 10%, about 12%, about 14%,about 16%, or about 18%. In some embodiments, the carrier comprisesmannitol in the composition at most about 12%, about 14%, about 16%,about 18%, or about 20%.

Other embodiments are also possible. While only specific neutralizingagents, food grade acids and food grade bases have been mentionedherein, other neutralizing agents, food grade acids and food grade basesmay be used.

In some embodiments, the excipient is a carrier, a flowability agent, apreservative or any combination selected therefrom. The amount ofexcipient in the composition will vary depending on the desired amountof the psychoactive alkaloid extract in the composition, and on theconcentration of psychoactive alkaloids in the extract. It will alsodepend on the degree of flowability required and the stability required.

In some embodiments, the excipients include a flowability agent, in anamount up to 2% by weight of the composition. Above 2%, little extrabenefit is gained. In other embodiments, the excipients include aflowability agent in a concentration equal to or less than 2% by weightof the composition. In some embodiments, the flowability agent ispresent in the composition at, by weight, about 0.1% to about 2%. Insome embodiments, the flowability agent is present in the compositionat, by weight, about 2% to about 1.75%, about 2% to about 1.5%, about 2%to about 1.25%, about 2% to about 1%, about 2% to about 0.75%, about 2%to about 0.5%, about 2% to about 0.25%, about 2% to about 0.1%, about1.75% to about 1.5%, about 1.75% to about 1.25%, about 1.75% to about1%, about 1.75% to about 0.75%, about 1.75% to about 0.5%, about 1.75%to about 0.25%, about 1.75% to about 0.1%, about 1.5% to about 1.25%,about 1.5% to about 1%, about 1.5% to about 0.75%, about 1.5% to about0.5%, about 1.5% to about 0.25%, about 1.5% to about 0.1%, about 1.25%to about 1%, about 1.25% to about 0.75%, about 1.25% to about 0.5%,about 1.25% to about 0.25%, about 1.25% to about 0.1%, about 1% to about0.75%, about 1% to about 0.5%, about 1% to about 0.25%, about 1% toabout 0.1%, about 0.75% to about 0.5%, about 0.75% to about 0.25%, about0.75% to about 0.1%, about 0.5% to about 0.25%, about 0.5% to about0.1%, or about 0.25% to about 0.1%. In some embodiments, the flowabilityagent is present in the composition at, by weight, about 2%, about1.75%, about 1.5%, about 1.25%, about 1%, about 0.75%, about 0.5%, about0.25%, or about 0.1%. In some embodiments, the flowability agent ispresent in the composition at, by weight, at least about 2%, about1.75%, about 1.5%, about 1.25%, about 1%, about 0.75%, about 0.5%, orabout 0.25%. In some embodiments, the flowability agent is present inthe composition at, by weight, at most about 1.75%, about 1.5%, about1.25%, about 1%, about 0.75%, about 0.5%, about 0.25%, or about 0.1%.

In some embodiments, the flowability agent is silicon dioxide. In otherembodiments, the flowability agent is magnesium stearate, stearic acidor talc, or is selected from any other known, suitable flowabilityagent. A combination of any of these flowability agents may be used. Itis also envisaged that other flowability agents can be used. Theimpurities present in the extract tend to have a negative effect on theflowability, and flow agents are added to counter these effects. Whilethere are known methods of measuring flowability, this is not alwaysnecessary as the product's lack of adequate flowability is often veryevident when one handles the product.

In some embodiments, the excipients include a carrier, in an amount upto 94% by weight of the composition. In some embodiments, the excipientsinclude a carrier ranging from 10-94% by weight of the composition. Insome embodiments, the carrier is present in the composition at, byweight, about 10% to about 94%. In some embodiments, the carrier ispresent in the composition at, by weight, about 10% to about 20%, about10% to about 30%, about 10% to about 40%, about 10% to about 50%, about10% to about 60%, about 10% to about 70%, about 10% to about 80%, about10% to about 90%, about 10% to about 94%, about 20% to about 30%, about20% to about 40%, about 20% to about 50%, about 20% to about 60%, about20% to about 70%, about 20% to about 80%, about 20% to about 90%, about20% to about 94%, about 30% to about 40%, about 30% to about 50%, about30% to about 60%, about 30% to about 70%, about 30% to about 80%, about30% to about 90%, about 30% to about 94%, about 40% to about 50%, about40% to about 60%, about 40% to about 70%, about 40% to about 80%, about40% to about 90%, about 40% to about 94%, about 50% to about 60%, about50% to about 70%, about 50% to about 80%, about 50% to about 90%, about50% to about 94%, about 60% to about 70%, about 60% to about 80%, about60% to about 90%, about 60% to about 94%, about 70% to about 80%, about70% to about 90%, about 70% to about 94%, about 80% to about 90%, about80% to about 94%, or about 90% to about 94%. In some embodiments, thecarrier is present in the composition at, by weight, about 10%, about20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%,about 90%, or about 94%. In some embodiments, the carrier is present inthe composition at, by weight, at least about 10%, about 20%, about 30%,about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%. Insome embodiments, the carrier is present in the composition at, byweight, at most about 20%, about 30%, about 40%, about 50%, about 60%,about 70%, about 80%, about 90%, or about 94%.

In some embodiments, the carrier is mannitol, maltodextrin, or in otherembodiments it is microcrystalline cellulose, coconut flour or cornstarch, or any other known, suitable carrier. A combination of any ofthese carriers may be used. It is also envisaged that other carriers canbe used.

The preservative is selected from ascorbic acid, citric acid, lactose,vitamin A, vitamin E, retinyl palmitate, selenium, sodium citrate,sodium ascorbate, calcium ascorbate, sodium benzoate, and potassiumbenzoate. A combination of any of these preservatives may be used. It isalso envisaged that other preservatives can be used.

In some embodiments, the excipients include a preservative, up to 10% byweight of the composition. In some embodiments, preservatives are notadded to the composition. There may be cases where a preservative is notrequired, or not wanted in the final product, and the concentration ofpreservative will be 0%. At a certain point (>10% in this example), thepreservative will not give any further benefit, and so the upper limitof preservative is 10%. In some embodiments, the preservatives arepresent in the composition at, by weight, about 0.1% to about 10%. Insome embodiments, the preservatives are present in the composition at,by weight, about 10% to about 9%, about 10% to about 8%, about 10% toabout 7%, about 10% to about 6%, about 10% to about 5%, about 10% toabout 4%, about 10% to about 3%, about 10% to about 2%, about 10% toabout 1%, about 10% to about 0.5%, about 10% to about 0.1%, about 9% toabout 8%, about 9% to about 7%, about 9% to about 6%, about 9% to about5%, about 9% to about 4%, about 9% to about 3%, about 9% to about 2%,about 9% to about 1%, about 9% to about 0.5%, about 9% to about 0.1%,about 8% to about 7%, about 8% to about 6%, about 8% to about 5%, about8% to about 4%, about 8% to about 3%, about 8% to about 2%, about 8% toabout 1%, about 8% to about 0.5%, about 8% to about 0.1%, about 7% toabout 6%, about 7% to about 5%, about 7% to about 4%, about 7% to about3%, about 7% to about 2%, about 7% to about 1%, about 7% to about 0.5%,about 7% to about 0.1%, about 6% to about 5%, about 6% to about 4%,about 6% to about 3%, about 6% to about 2%, about 6% to about 1%, about6% to about 0.5%, about 6% to about 0.1%, about 5% to about 4%, about 5%to about 3%, about 5% to about 2%, about 5% to about 1%, about 5% toabout 0.5%, about 5% to about 0.1%, about 4% to about 3%, about 4% toabout 2%, about 4% to about 1%, about 4% to about 0.5%, about 4% toabout 0.1%, about 3% to about 2%, about 3% to about 1%, about 3% toabout 0.5%, about 3% to about 0.1%, about 2% to about 1%, about 2% toabout 0.5%, about 2% to about 0.1%, about 1% to about 0.5%, about 1% toabout 0.1%, or about 0.5% to about 0.1%. In some embodiments, thepreservatives are present in the composition at, by weight, about 10%,about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%,about 2%, about 1%, about 0.5%, or about 0.1%. In some embodiments, thepreservatives are present in the composition at, by weight, at leastabout 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%,about 3%, about 2%, about 1%, or about 0.5%. In some embodiments, thepreservatives are present in the composition at, by weight, at mostabout 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%,about 2%, about 1%, about 0.5%, or about 0.1%.

In some embodiments, a psychoactive alkaloid composition comprises oneor more preservatives up to 10%.

In some embodiments, a first preservative of the one or morepreservatives is present in the composition from about 0.1% to about 3%.In some embodiments, a first preservative of the one or morepreservatives is present in the composition from about 0.1% to about0.5%, about 0.1% to about 0.9%, about 0.1% to about 1.3%, about 0.1% toabout 1.7%, about 0.1% to about 2.1%, about 0.1% to about 2.4%, about0.1% to about 2.7%, about 0.1% to about 3%, about 0.5% to about 0.9%,about 0.5% to about 1.3%, about 0.5% to about 1.7%, about 0.5% to about2.1%, about 0.5% to about 2.4%, about 0.5% to about 2.7%, about 0.5% toabout 3%, about 0.9% to about 1.3%, about 0.9% to about 1.7%, about 0.9%to about 2.1%, about 0.9% to about 2.4%, about 0.9% to about 2.7%, about0.9% to about 3%, about 1.3% to about 1.7%, about 1.3% to about 2.1%,about 1.3% to about 2.4%, about 1.3% to about 2.7%, about 1.3% to about3%, about 1.7% to about 2.1%, about 1.7% to about 2.4%, about 1.7% toabout 2.7%, about 1.7% to about 3%, about 2.1% to about 2.4%, about 2.1%to about 2.7%, about 2.1% to about 3%, about 2.4% to about 2.7%, about2.4% to about 3%, or about 2.7% to about 3%. In some embodiments, afirst preservative of the one or more preservatives is present in thecomposition from about 0.1%, about 0.5%, about 0.9%, about 1.3%, about1.7%, about 2.1%, about 2.4%, about 2.7%, or about 3%. In someembodiments, a first preservative of the one or more preservatives ispresent in the composition from at least about 0.1%, about 0.5%, about0.9%, about 1.3%, about 1.7%, about 2.1%, about 2.4%, or about 2.7%. Insome embodiments, a first preservative of the one or more preservativesis present in the composition from at most about 0.5%, about 0.9%, about1.3%, about 1.7%, about 2.1%, about 2.4%, about 2.7%, or about 3%.

In some embodiments, a first preservative of the one or morepreservatives is present in the composition from about 0.1% to about 2%.In some embodiments, a first preservative of the one or morepreservatives is present in the composition from about 0.1% to about0.3%, about 0.1% to about 0.5%, about 0.1% to about 0.7%, about 0.1% toabout 0.9%, about 0.1% to about 1.1%, about 0.1% to about 1.3%, about0.1% to about 1.5%, about 0.1% to about 1.7%, about 0.1% to about 2%,about 0.3% to about 0.5%, about 0.3% to about 0.7%, about 0.3% to about0.9%, about 0.3% to about 1.1%, about 0.3% to about 1.3%, about 0.3% toabout 1.5%, about 0.3% to about 1.7%, about 0.3% to about 2%, about 0.5%to about 0.7%, about 0.5% to about 0.9%, about 0.5% to about 1.1%, about0.5% to about 1.3%, about 0.5% to about 1.5%, about 0.5% to about 1.7%,about 0.5% to about 2%, about 0.7% to about 0.9%, about 0.7% to about1.1%, about 0.7% to about 1.3%, about 0.7% to about 1.5%, about 0.7% toabout 1.7%, about 0.7% to about 2%, about 0.9% to about 1.1%, about 0.9%to about 1.3%, about 0.9% to about 1.5%, about 0.9% to about 1.7%, about0.9% to about 2%, about 1.1% to about 1.3%, about 1.1% to about 1.5%,about 1.1% to about 1.7%, about 1.1% to about 2%, about 1.3% to about1.5%, about 1.3% to about 1.7%, about 1.3% to about 2%, about 1.5% toabout 1.7%, about 1.5% to about 2%, or about 1.7% to about 2%. In someembodiments, a first preservative of the one or more preservatives ispresent in the composition from about 0.1%, about 0.3%, about 0.5%,about 0.7%, about 0.9%, about 1.1%, about 1.3%, about 1.5%, about 1.7%,or about 2%. In some embodiments, a first preservative of the one ormore preservatives is present in the composition from at least about0.1%, about 0.3%, about 0.5%, about 0.7%, about 0.9%, about 1.1%, about1.3%, about 1.5%, or about 1.7%. In some embodiments, a firstpreservative of the one or more preservatives is present in thecomposition from at most about 0.3%, about 0.5%, about 0.7%, about 0.9%,about 1.1%, about 1.3%, about 1.5%, about 1.7%, or about 2%.

In some embodiments, a second preservative of the one or morepreservatives is present in the composition from about 0.1% to about 2%.In some embodiments, a second preservative of the one or morepreservatives is present in the composition from about 0.1% to about0.3%, about 0.1% to about 0.5%, about 0.1% to about 0.7%, about 0.1% toabout 0.9%, about 0.1% to about 1.1%, about 0.1% to about 1.3%, about0.1% to about 1.5%, about 0.1% to about 1.7%, about 0.1% to about 2%,about 0.3% to about 0.5%, about 0.3% to about 0.7%, about 0.3% to about0.9%, about 0.3% to about 1.1%, about 0.3% to about 1.3%, about 0.3% toabout 1.5%, about 0.3% to about 1.7%, about 0.3% to about 2%, about 0.5%to about 0.7%, about 0.5% to about 0.9%, about 0.5% to about 1.1%, about0.5% to about 1.3%, about 0.5% to about 1.5%, about 0.5% to about 1.7%,about 0.5% to about 2%, about 0.7% to about 0.9%, about 0.7% to about1.1%, about 0.7% to about 1.3%, about 0.7% to about 1.5%, about 0.7% toabout 1.7%, about 0.7% to about 2%, about 0.9% to about 1.1%, about 0.9%to about 1.3%, about 0.9% to about 1.5%, about 0.9% to about 1.7%, about0.9% to about 2%, about 1.1% to about 1.3%, about 1.1% to about 1.5%,about 1.1% to about 1.7%, about 1.1% to about 2%, about 1.3% to about1.5%, about 1.3% to about 1.7%, about 1.3% to about 2%, about 1.5% toabout 1.7%, about 1.5% to about 2%, or about 1.7% to about 2%. In someembodiments, a second preservative of the one or more preservatives ispresent in the composition from about 0.1%, about 0.3%, about 0.5%,about 0.7%, about 0.9%, about 1.1%, about 1.3%, about 1.5%, about 1.7%,or about 2%. In some embodiments, a second preservative of the one ormore preservatives is present in the composition from at least about0.1%, about 0.3%, about 0.5%, about 0.7%, about 0.9%, about 1.1%, about1.3%, about 1.5%, or about 1.7%. In some embodiments, a secondpreservative of the one or more preservatives is present in thecomposition from at most about 0.3%, about 0.5%, about 0.7%, about 0.9%,about 1.1%, about 1.3%, about 1.5%, about 1.7%, or about 2%.

The main consideration is that, depending on the source material'sconcentration and the efficiency of the extraction, the concentration ofthe extract needs to be blended down to the required value ofstandardization. This dictates the amount of excipient for each batch,which may be different. Therefore, the amount of excipient that can beadded can be anywhere between say 0.100% to 99.9%, depending on thesource concentration before blending. The other excipient components maybe held relatively constant between batches, or within a much narrowerrange (i.e., 0-2% flowability agent, 0-10% preservative, 0-0.5%antioxidant, or 0-0.5% bioavailability agent).

C. Apparatus

Referring to FIG. 8 , an example of the apparatus is shownschematically. Raw psilocybin mushrooms are provided in a hopper 800,for example, and are released in batches into container 801. The rawfungal material is then dried in a forced air oven 802. The driedbiomass is placed into a grinder 803 for grinding.

After the drying and grinding steps, the ground biomass is placed in anagitated, heat-controlled extraction vessel 805. The vessel holds thebiomass and solvent 806, such as lower aliphatic alcohols, water,buffered acid or buffered alkaline, or a mixture thereof. The vessel maybe surrounded by an insulating wall 804. Alternately, there may be aninsulating jacket wrapped around the vessel. The insulating wall 804 orjacket helps to maintain the contents 806 under a constant temperature(T) between 5-95° C. The pressure (P) inside the extraction vessel 805may be regulated up to 100 MPa (15000 psig).

After the extraction, the bottom of the extraction vessel 805 is openedat outlet 807, and the extraction slurry is collected in container 808.The extraction slurry is then fed into filter 809. After filtration, thefirst filtrate leaves the filter 809 and is collected in container 810.The first filtrate residue 811 is then fed back at R into agitated,heat-controlled vessel 805 and more solvent (S) is added. After thesecond extraction, the extraction slurry is collected in container 808and is then fed into filter 812 (or filter 809). After filtration, thesecond filtrate and solvent mixture leaves the filter 812 and iscollected in container 813.

After the two filtration stages, if there are two, the filtrates aremixed in container 814. Otherwise, if there is only a single filtrationstep, mixing is unnecessary. Neutralizer is added as necessary to thefiltrate in container 814. The extraction slurry, pH-adjusted wherenecessary, is then passed to rotary evaporator 815 in which all or partof the solvent is evaporated, depending on the embodiment. If all thesolvent is evaporated, then reverse osmosis water is added to the solidsremaining after the evaporation.

The concentrated slurry is then passed to container 816 and tested todetermine its alkaloid content, using a titration setup 817. Carriersare added to container 816 with the concentrated slurry, and mixed. Thestandardized slurry is then placed in a bench-top spray drier 818 toproduce psilocybin mushroom extract that is collected in container 819.

Referring to FIG. 13 , an example of the apparatus is shownschematically. Raw Psilocybe cubensis mushrooms are added to a hopper1300 and then released in batches into container 1301. The raw fungalmaterial is then dried in a forced air oven 1302 to result in driedbiomass. The dried biomass is placed into a grinder 1303 for grinding.

The dried powdered biomass is placed into a heat-controlled vessel 1305,and solvent (S) is added to the heat-controlled vessel. The vessel 1305is surrounded by an insulating wall 1304. Alternately, an insulatingjacket may be wrapped around the vessel. The insulating wall 1304 orjacket helps to maintain the contents 1306 under a constant temperature(T) between 5-95° C. The pressure (P) inside the extraction vessel 1305may be regulated up to 100 MPa (15,000 psig).

After the extraction, the bottom of the extraction vessel 1305 wasopened at outlet 1307 and the extraction slurry was collected in acontainer 1308. The extraction slurry was then fed into a filter 1309and a first filtrate was collected in container 1310. The first filtrateresidue 1311 was then fed back (R) into the agitated, heat-controlledvessel 1305 and more solvent (S) was added for a second extraction.After the second extraction, the extraction slurry was collected in thecontainer 1308 and was then fed into a filter 1312. After filtration,the obtained second filtrate was collected in container 1313.

After the two filtration stages, the filtrates were mixed in container1314 to obtain a bulk filtrate. In other embodiments, if there is only asingle filtration step, this mixing step is not required.

The bulk filtrate is placed in a rotary evaporator 1315, and part of thesolvent is evaporated from the bulk filtrate. The resultant extract istransferred to a container 1316, where the pH of the extract isadjusted, followed by centrifugation 1317 to remove the solidprecipitates. The resultant supernatant is loaded onto a column 1318 ofresin. An initial wash is given to the column with a solvent to removeimpurities from the resin, and fraction 1319 is collected. A second washis given to the column with another solvent to elute the psychoactivealkaloids from the column and results in fraction 1320. A final wash isgiven to the column with another solvent to wash any impurities from thecolumn and to prepare the column for use again, and the fraction 1321 isobtained. The elution fraction 1320 with the psychoactive alkaloids isthen concentrated in a rotary evaporator 1322 to result in the purifiedpsychoactive alkaloid solution.

In a container 1323 the purified psychoactive alkaloid solution anddesired excipients are added together and thoroughly mixed to result ina final standardized slurry having a specified concentration ofalkaloids. The final standardized slurry is then subjected tospray-drying 1324 to obtain a final powdered alkaloid extract 1325 witha total psilocybin/psilocin concentration defined as a percentage to twodecimal places or two significant figures by dry weight.

In other embodiments, parts of the apparatus may be reused orduplicated. For example, if desired, the elution fraction 1320 may bereloaded into the container 1316 for pH adjustment, and the steps fromthereon can be repeated to allow for further purification of theobtained purified psychoactive alkaloid solution.

Referring to FIG. 17 , an example of the apparatus is shownschematically. Raw Psilocybe cubensis mushrooms are added to a hopper1700 and released in batches into container 1701. The raw fungalmaterial is then dried in a forced air oven 1702 to result in driedbiomass. The dried biomass is placed into a grinder 1703 for grinding.

The dried powdered biomass is placed into a heat-controlled vessel 1705,and solvent (S) is added to the heat-controlled vessel. The vessel 1705is surrounded by an insulating wall 1704. Alternately, an insulatingjacket can be wrapped around the vessel. The insulating wall 1704 orjacket helps to maintain the contents 1706 under a constant temperature(T) between 5-95° C. The pressure (P) inside the extraction vessel 1705may be regulated up to 100 MPa (15,000 psig).

After the extraction, the bottom of the extraction vessel 1705 is openedat outlet 1707 and the extraction slurry is collected in a container1708. The extraction slurry is then fed into a filter 1709, and a firstfiltrate is collected in container 1710. The first filtrate residue 1711is then fed back (R) into the agitated, heat-controlled vessel 1705, andmore solvent (S) is added for a second extraction. After the secondextraction, the extraction slurry is collected in the container 1708 andis then fed into a filter 1712. After filtration, the obtained secondfiltrate is collected in container 1713.

After the two filtration stages, the filtrates are mixed in container1714 to obtain a bulk filtrate. In other embodiments, if there is only asingle filtration step, this mixing step is not required.

The bulk filtrate was placed in a rotary evaporator 1715, and part ofthe solvent is evaporated from the bulk filtrate. The resultant extractis transferred to a container 1716, where the pH of the extract isadjusted, followed by centrifugation 1717 to remove the solidprecipitates. The resultant supernatant is loaded onto a column 1718 ofresin. An initial wash is given to the column with a solvent to removeimpurities from the resin, and fraction 1719 is collected. A second washis given to the column with another solvent to elute the psychoactivealkaloids from the column and result in fraction 1720. A final wash isgiven to the column with another solvent to wash any impurities from thecolumn and to prepare the column for use again, and the fraction 1721was obtained. The elution fraction 1720 with the psychoactive alkaloidsis then concentrated in a rotary evaporator 1722 to result in thepurified psychoactive alkaloid extract.

In a container 1723 the purified psychoactive alkaloid extract anddesired excipients are added together and thoroughly mixed to result ina final standardized slurry having a specific amount of alkaloids. Thefinal standardized slurry is then subjected to spray-drying 1724 toobtain a final powdered composition 1725 with a totalpsilocybin/psilocin concentration defined as a percentage to two decimalplaces or two significant figures by dry weight.

In other embodiments, parts of the apparatus may be reused orduplicated. For example, if desired, the elution fraction 1720 may bereloaded into the container 1716 for pH adjustment, and the steps fromthereon can be repeated to allow for further purification of theobtained purified psychoactive alkaloid extract.

In one embodiment, the psychoactive alkaloid extract is obtained afterevaporating the solvent from the bulk filtrate. The psychoactivealkaloid extract is transferred to a container 1723, and desiredexcipients are added together, and thoroughly mixed to result in a finalstandardized slurry having a specific amount of alkaloids. The finalstandardized slurry is then subjected to spray-drying 1724 to obtain afinal powdered composition 1725 with a total psilocybin/psilocinconcentration defined as a percentage to two decimal places or twosignificant figures by dry weight.

Referring to FIG. 23 , an example of the apparatus is shownschematically. Raw Psilocybe cubensis mushrooms are added to a hopper2300 and then released in batches into container 2301. The raw fungalmaterial is then dried in a forced air oven 2302 to result in the driedbiomass. The dried biomass is placed into a grinder 2303 for grinding toresult in dried powdered biomass.

The dried powdered biomass is placed into a heat-controlled vessel 2305,and acidified/basified solvent (S) is added to the vessel to obtain aspecific pH (lower than 3.5 or greater than 10.5). The vessel 2305 issurrounded by an insulating wall 2304. Alternately, an insulating jacketmay be wrapped around the vessel. The insulating wall 108 or jackethelps to maintain the contents 2306 under a constant temperature (T)between 5-95° C. The pressure (P) inside the extraction vessel 2305 maybe regulated from 7 to 20,000 psi. The extraction is performed with asolvent to solid (dried powdered biomass) proportion in the range of 1L:1 kg to 50 L:1 kg.

After the extraction, the bottom of the extraction vessel 2305 is openedat outlet 2307, and the extraction slurry is collected in a container2308. The extraction slurry is then fed into a filter 2309, and a firstfiltrate is collected in container 2310. The first filtrate residue 2311is then fed back (R) into the agitated, heat-controlled vessel 2305, andmore solvent (S) is added for a second extraction. After the secondextraction, the extraction slurry is collected in the container 2308 andthen fed into a filter 2312. After filtration, the obtained secondfiltrate is collected in container 2313.

After the two filtration stages, the filtrates are mixed in container2314 to obtain a mixed filtrate, i.e., the psychoactive alkaloid liquid.In other embodiments, if there is only a single filtration step, thismixing step is not required. By adding an acid or a base, the pH of thepsychoactive alkaloid liquid is brought to a pH ranging from 3.5-4.5.

The pH-adjusted, mixed filtrate is then placed in a rotary evaporator2315, and part of the solvent is evaporated from the mixed filtrate toform the psychoactive alkaloid extract, which is here a slurry.

For obtaining the psychoactive alkaloid composition, the evaporation inthe rotary evaporator 2315 is stopped after a desired portion of solventis evaporated. The resultant slurry is transferred to a container 2316where a measured quantity of one or more excipients is added to obtain astandardized slurry. The obtained standardized slurry is dried in afreeze dryer 2317 to obtain the psychoactive alkaloid composition.

In other embodiments, parts of the apparatus may be reused orduplicated. For example, if desired, for further extraction, thefiltrate residue may be reloaded into the extraction vessel 2305, andthe obtained filtrate can be added to mixed filtrate container of 2314,and the steps from thereon can be repeated to obtain the psychoactivealkaloid extract.

D. Extraction

Extraction Process 1

Referring to FIG. 1 , a flowchart is shown of the basic steps of theextraction process for extracting psychoactive compounds frompsychedelic fungus. In step 100, a solvent is added to a biomass ofdried and ground, raw psychedelic fungus. The raw psychedelic fungusincludes psilocybin fungi, including Psilocybe cubensis mushrooms,Psilocybe cyanescens mushrooms, Amanita muscaria mushrooms or a mixtureof these. Other species of psychedelic mushrooms may also be used.

The parts of the mushrooms used include, for example, caps, gills,stems, and hyphae, and more particularly, any part of the psilocybinmushroom or mycelium can be included. In other cases, the rawpsychedelic fungus parts used include only caps, or only stems, or onlygills, or only hyphae or only mycelium or any mixture thereof. In stillother cases, parts of the raw psychedelic fungus used are those thatwould normally be considered waste, in which valuable psychoactivecompounds are found only in lower concentrations. The mushroom parts maybe ground using a milling machine or pulverization device, for example.

Ideally, the moisture content of the raw plant material after drying islow compared to the total dried biomass weight. For example, themoisture content may be under 5% for smaller scale extractions and under10% for larger scale extractions. Wet mushrooms, e.g. with a moistureabove 80%, may degrade rapidly. Dried biomass lends itself well toextraction since the drying process usually breaks down cell walls,allowing solvent to capture the molecules inside. The temperature of theoven and the drying time depend on how much moisture is in the rawpsychedelic fungus, and on the quantity of raw psychedelic fungus.

The solvent may be selected from a range of different solvents,including lower aliphatic alcohols (C=1, 2, 3 or 4), water,alcohol-water mixtures, strong alkaline buffers, and strong acidicbuffers. A wide range of solvent to solid ratios can be used. Typically,a 1 to 50:1 solvent-solid ratio (L:kg) may be used for the extraction.The amount of solvent used generally varies according to the weight ofthe raw psychedelic fungus.

In step 110, as a result of adding the solvent and soaking the biomassof dried, raw psychedelic fungus in the solvent, essential elements orpsychoactive alkaloids found in the biomass, dissolve into the solvent.The solvent may be at a low or high temperature, and pressure may beapplied to the solvent. In some embodiments the solvent is at roomtemperature. The optimal temperature of extraction varies depending onthe solvent type used for the process. However, the optimal temperaturefor extraction is in range of 5-95° C. The useful temperature rangespans most of the liquid state of the solvent used, and upper and lowerlimits are determined by physical practicalities and limits of theavailable apparatus. Still, the temperature of the solvent may beoutside of this range in other embodiments. The duration of theextraction is from 10 minutes to 12 hours, with or without agitation.Optimum duration is determined by experimentation and depends on thechosen solvent and the strength of agitation in the extraction vessel.

If pressure is applied, it may be in the range of 50 kPa-100 MPa aboveatmospheric (7-15000 psig). The lower limit of pressure is indicative ofwhen a benefit is seen in the rate at which the psychoactive alkaloidsdissolve in the solvent, since the increased pressure may increase thereaction kinetics of the dissolution of the psychoactive alkaloids intothe solvent. The upper limit is determined by what is physicallypractical given the constraints of equipment to safely operate underhigh pressure. Nevertheless, other pressures may be used. Solventcomposition, particle size, and extraction temperature may determine howmuch pressure needs to be applied.

In some embodiments, the biomass of the psychoactive organism is reducedto a particle size of 6 millimeters (mm) to 0.03 mm prior to contactingwith the solvent. In some embodiments, prior to contacting with thesolvent, the biomass of the psychoactive organism is reduced to aparticle size of about 0.03 mm to about 6 mm. In some embodiments, priorto contacting with the solvent, the biomass of the psychoactive organismis reduced to a particle size of about 6 mm to about 5 mm, about 6 mm toabout 4 mm, about 6 mm to about 3 mm, about 6 mm to about 2 mm, about 6mm to about 1 mm, about 6 mm to about 0.5 mm, about 6 mm to about 0.1mm, about 6 mm to about 0.05 mm, about 6 mm to about 0.03 mm, about 5 mmto about 4 mm, about 5 mm to about 3 mm, about 5 mm to about 2 mm, about5 mm to about 1 mm, about 5 mm to about 0.5 mm, about 5 mm to about 0.1mm, about 5 mm to about 0.05 mm, about 5 mm to about 0.03 mm, about 4 mmto about 3 mm, about 4 mm to about 2 mm, about 4 mm to about 1 mm, about4 mm to about 0.5 mm, about 4 mm to about 0.1 mm, about 4 mm to about0.05 mm, about 4 mm to about 0.03 mm, about 3 mm to about 2 mm, about 3mm to about 1 mm, about 3 mm to about 0.5 mm, about 3 mm to about 0.1mm, about 3 mm to about 0.05 mm, about 3 mm to about 0.03 mm, about 2 mmto about 1 mm, about 2 mm to about 0.5 mm, about 2 mm to about 0.1 mm,about 2 mm to about 0.05 mm, about 2 mm to about 0.03 mm, about 1 mm toabout 0.5 mm, about 1 mm to about 0.1 mm, about 1 mm to about 0.05 mm,about 1 mm to about 0.03 mm, about 0.5 mm to about 0.1 mm, about 0.5 mmto about 0.05 mm, about 0.5 mm to about 0.03 mm, about 0.1 mm to about0.05 mm, about 0.1 mm to about 0.03 mm, or about 0.05 mm to about 0.03mm. In some embodiments, prior to contacting with the solvent, thebiomass of the psychoactive organism is reduced to a particle size ofabout 6 mm, about 5 mm, about 4 mm, about 3 mm, about 2 mm, about 1 mm,about 0.5 mm, about 0.1 mm, about 0.05 mm, or about 0.03 mm. In someembodiments, prior to contacting with the solvent, the biomass of thepsychoactive organism is reduced to a particle size of at least about 6mm, about 5 mm, about 4 mm, about 3 mm, about 2 mm, about 1 mm, about0.5 mm, about 0.1 mm, or about 0.05 mm. In some embodiments, prior tocontacting with the solvent, the biomass of the psychoactive organism isreduced to a particle size of at most about 5 mm, about 4 mm, about 3mm, about 2 mm, about 1 mm, about 0.5 mm, about 0.1 mm, about 0.05 mm,or about 0.03 mm.

In some embodiments, the biomass of the psychoactive organism is reducedto a particle size of 1 millimeters (mm) to 0.03 mm prior to contactingwith the solvent. In some embodiments, prior to contacting with thesolvent, the biomass of the psychoactive organism is reduced to aparticle size of about 0.03 mm to about 1 mm. In some embodiments, priorto contacting with the solvent, the biomass of the psychoactive organismis reduced to a particle size of about 1 mm to about 0.9 mm, about 1 mmto about 0.8 mm, about 1 mm to about 0.7 mm, about 1 mm to about 0.6 mm,about 1 mm to about 0.5 mm, about 1 mm to about 0.4 mm, about 1 mm toabout 0.3 mm, about 1 mm to about 0.2 mm, about 1 mm to about 0.1 mm,about 1 mm to about 0.05 mm, about 1 mm to about 0.03 mm, about 0.9 mmto about 0.8 mm, about 0.9 mm to about 0.7 mm, about 0.9 mm to about 0.6mm, about 0.9 mm to about 0.5 mm, about 0.9 mm to about 0.4 mm, about0.9 mm to about 0.3 mm, about 0.9 mm to about 0.2 mm, about 0.9 mm toabout 0.1 mm, about 0.9 mm to about 0.05 mm, about 0.9 mm to about 0.03mm, about 0.8 mm to about 0.7 mm, about 0.8 mm to about 0.6 mm, about0.8 mm to about 0.5 mm, about 0.8 mm to about 0.4 mm, about 0.8 mm toabout 0.3 mm, about 0.8 mm to about 0.2 mm, about 0.8 mm to about 0.1mm, about 0.8 mm to about 0.05 mm, about 0.8 mm to about 0.03 mm, about0.7 mm to about 0.6 mm, about 0.7 mm to about 0.5 mm, about 0.7 mm toabout 0.4 mm, about 0.7 mm to about 0.3 mm, about 0.7 mm to about 0.2mm, about 0.7 mm to about 0.1 mm, about 0.7 mm to about 0.05 mm, about0.7 mm to about 0.03 mm, about 0.6 mm to about 0.5 mm, about 0.6 mm toabout 0.4 mm, about 0.6 mm to about 0.3 mm, about 0.6 mm to about 0.2mm, about 0.6 mm to about 0.1 mm, about 0.6 mm to about 0.05 mm, about0.6 mm to about 0.03 mm, about 0.5 mm to about 0.4 mm, about 0.5 mm toabout 0.3 mm, about 0.5 mm to about 0.2 mm, about 0.5 mm to about 0.1mm, about 0.5 mm to about 0.05 mm, about 0.5 mm to about 0.03 mm, about0.4 mm to about 0.3 mm, about 0.4 mm to about 0.2 mm, about 0.4 mm toabout 0.1 mm, about 0.4 mm to about 0.05 mm, about 0.4 mm to about 0.03mm, about 0.3 mm to about 0.2 mm, about 0.3 mm to about 0.1 mm, about0.3 mm to about 0.05 mm, about 0.3 mm to about 0.03 mm, about 0.2 mm toabout 0.1 mm, about 0.2 mm to about 0.05 mm, about 0.2 mm to about 0.03mm, about 0.1 mm to about 0.05 mm, about 0.1 mm to about 0.03 mm, orabout 0.05 mm to about 0.03 mm. In some embodiments, prior to contactingwith the solvent, the biomass of the psychoactive organism is reduced toa particle size of about 1 mm, about 0.9 mm, about 0.8 mm, about 0.7 mm,about 0.6 mm, about 0.5 mm, about 0.4 mm, about 0.3 mm, about 0.2 mm,about 0.1 mm, about 0.05 mm, or about 0.03 mm. In some embodiments,prior to contacting with the solvent, the biomass of the psychoactiveorganism is reduced to a particle size of at least about 1 mm, about 0.9mm, about 0.8 mm, about 0.7 mm, about 0.6 mm, about 0.5 mm, about 0.4mm, about 0.3 mm, about 0.2 mm, about 0.1 mm, or about 0.05 mm. In someembodiments, prior to contacting with the solvent, the biomass of thepsychoactive organism is reduced to a particle size of at most about 0.9mm, about 0.8 mm, about 0.7 mm, about 0.6 mm, about 0.5 mm, about 0.4mm, about 0.3 mm, about 0.2 mm, about 0.1 mm, about 0.05 mm, or about0.03 mm.

In some embodiments, the biomass of the psychoactive organism is reducedto a particle size of at least 0.074 mm prior to contacting with thesolvent.

The extraction results in an extraction slurry, which is formed ofundissolved and insoluble solids from the mixture of biomass andsolvent, which now carries dissolved extract. Some of the undissolvedsolids may be undesirable components.

In step 120, the extraction slurry is filtered, resulting in a residue(i.e., the undissolved portion of the biomass) and filtrate. Thefiltering step may be carried out with the extraction slurry still hot,or it may first be allowed to cool. The extraction and filtration stepsmay be repeated multiple times on the same residue, with a fresh batchof solvent, which may have the same composition as the first solvent, orit may be a different solvent.

In step 130, if the filtrate results from using a strongly acidic oralkaline solvent, then the filtrate is brought closer to neutral, e.g.,to a pH between 4 and 9 or thereabouts. Desirable effects, such as morecomplete extraction, preservation of the alkaloids from decomposition,or the ability to selectively extract certain specific alkaloids, areseen during the extraction stage when stronger acids or alkalis are usedcompared to weaker ones.

In step 140, evaporation of some or all of the solvent from the filtrateresults in a concentrated slurry 150 (liquid and solids) or just solids.If the solvent is methanol, then all of it is evaporated to reduce thelikelihood of toxicity. For other solvents, only some of the solventneeds to be evaporated. In the case where solids are obtained from theevaporation, water is added to the solids to form the concentratedslurry 150. The solids tend not to dissolve back into solution becausethey are less soluble in methanol and ethanol, for example, than water.Also, the solids may be less soluble in the colder water that is addedback than the warmer or hotter water that is used for the extraction.Another reason is saturation of the solution or that some of the solidsare irreversibly precipitated.

In step 160, standardization of the concentrated slurry takes place. Theaim is to stabilize the extract by adding stabilizer (e.g., ascorbicacid and silica), and then titrating with a carrier (e.g., maltodextrin)to result in a known concentration of psychoactive alkaloids. The slurryis analyzed for dry mass concentration and alkaloid content. The liquidcomponent of the concentrated slurry is first analyzed using aloss-on-drying analysis and high-performance liquid chromatographycoupled with diode array detection or mass spectrometry to determine thealkaloid content. Depending on the determined alkaloid content,non-toxic carriers are added to the concentrated slurry to provide adesired ratio between the weight of alkaloid and weight of carrier inthe concentrated slurry. The added carriers, blending agents,excipients, flow aids, etc., that may be used include maltodextrin fromcorn, potato, or tapioca, for example, gum arabic, silicon dioxide,microcrystalline cellulose, ascorbic acid, sodium benzoate, sodiumphosphate, sodium citrate, rice hulls, and rice. A combination of any ofthese carriers may be used.

In step 170, the concentrated slurry is dried to remove the remainingsolvent or water, resulting in a powdered psilocybin mushroom extractwith a known concentration by weight of psychoactive compound(s). Theextract is a powdered psilocybin mushroom extract that may have, forexample, a total psychoactive alkaloid concentration of 0.1-10% by dryweight. Other compounds may be included in the extract. These may besugars, proteins, carbohydrates, and fats, and may make up about half ofthe extract. Step 170 is optional, as it may be the intention to producea liquid extract instead of a powdered extract.

In some embodiments, the extraction is performed at a temperatureranging from 5-95° C. In some embodiments, the extraction is performedat a temperature ranging from about 5° C. to about 95° C. In someembodiments, the extraction is performed at a temperature ranging fromabout 5° C. to about 10° C., about 5° C. to about 20° C., about 5° C. toabout 30° C., about 5° C. to about 40° C., about 5° C. to about 50° C.,about 5° C. to about 60° C., about 5° C. to about 70° C., about 5° C. toabout 80° C., about 5° C. to about 90° C., about 5° C. to about 95° C.,about 10° C. to about 20° C., about 10° C. to about 30° C., about 10° C.to about 40° C., about 10° C. to about 50° C., about 10° C. to about 60°C., about 10° C. to about 70° C., about 10° C. to about 80° C., about10° C. to about 90° C., about 10° C. to about 95° C., about 20° C. toabout 30° C., about 20° C. to about 40° C., about 20° C. to about 50°C., about 20° C. to about 60° C., about 20° C. to about 70° C., about20° C. to about 80° C., about 20° C. to about 90° C., about 20° C. toabout 95° C., about 30° C. to about 40° C., about 30° C. to about 50°C., about 30° C. to about 60° C., about 30° C. to about 70° C., about30° C. to about 80° C., about 30° C. to about 90° C., about 30° C. toabout 95° C., about 40° C. to about 50° C., about 40° C. to about 60°C., about 40° C. to about 70° C., about 40° C. to about 80° C., about40° C. to about 90° C., about 40° C. to about 95° C., about 50° C. toabout 60° C., about 50° C. to about 70° C., about 50° C. to about 80°C., about 50° C. to about 90° C., about 50° C. to about 95° C., about60° C. to about 70° C., about 60° C. to about 80° C., about 60° C. toabout 90° C., about 60° C. to about 95° C., about 70° C. to about 80°C., about 70° C. to about 90° C., about 70° C. to about 95° C., about80° C. to about 90° C., about 80° C. to about 95° C., or about 90° C. toabout 95° C. In some embodiments, the extraction is performed at atemperature ranging from about 5° C., about 10° C., about 20° C., about30° C., about 40° C., about 50° C., about 60° C., about 70° C., about80° C., about 90° C., or about 95° C. In some embodiments, theextraction is performed at a temperature ranging from at least about 5°C., about 10° C., about 20° C., about 30° C., about 40° C., about 50°C., about 60° C., about 70° C., about 80° C., or about 90° C. In someembodiments, the extraction is performed at a temperature ranging fromat most about 10° C., about 20° C., about 30° C., about 40° C., about50° C., about 60° C., about 70° C., about 80° C., about 90° C., or about95° C.

In other embodiments, the extraction is performed at a temperatureranging from 50−75° C. In some embodiments, the extraction is performedat a temperature ranging from about 50° C. to about 75° C. In someembodiments, the extraction is performed at a temperature ranging fromabout 50° C. to about 55° C., about 50° C. to about 60° C., about 50° C.to about 65° C., about 50° C. to about 70° C., about 50° C. to about 75°C., about 55° C. to about 60° C., about 55° C. to about 65° C., about55° C. to about 70° C., about 55° C. to about 75° C., about 60° C. toabout 65° C., about 60° C. to about 70° C., about 60° C. to about 75°C., about 65° C. to about 70° C., about 65° C. to about 75° C., or about70° C. to about 75° C. In some embodiments, the extraction is performedat a temperature ranging from about 50° C., about 55° C., about 60° C.,about 65° C., about 70° C., or about 75° C. In some embodiments, theextraction is performed at a temperature ranging from at least about 50°C., about 55° C., about 60° C., about 65° C., or about 70° C. In someembodiments, the extraction is performed at a temperature ranging fromat most about 55° C., about 60° C., about 65° C., about 70° C., or about75° C.

In some embodiments, the extraction is performed for a time periodranging from 10-720 minutes. For most cases, a time below 10 min wouldresult in a mostly incomplete yield, and above 720 min the extractionmay be incomplete but would be continuing at a negligible rate. In someembodiments, the extraction is performed for a time period ranging fromabout 10 min to about 720 min. In some embodiments, the extraction isperformed for a time period ranging from about 10 min to about 100 min,about 10 min to about 200 min, about 10 min to about 300 min, about 10min to about 400 min, about 10 min to about 500 min, about 10 min toabout 600 min, about 10 min to about 720 min, about 100 min to about 200min, about 100 min to about 300 min, about 100 min to about 400 min,about 100 min to about 500 min, about 100 min to about 600 min, about100 min to about 720 min, about 200 min to about 300 min, about 200 minto about 400 min, about 200 min to about 500 min, about 200 min to about600 min, about 200 min to about 720 min, about 300 min to about 400 min,about 300 min to about 500 min, about 300 min to about 600 min, about300 min to about 720 min, about 400 min to about 500 min, about 400 minto about 600 min, about 400 min to about 720 min, about 500 min to about600 min, about 500 min to about 720 min, or about 600 min to about 720min. In some embodiments, the extraction is performed for a time periodranging from about 10 min, about 100 min, about 200 min, about 300 min,about 400 min, about 500 min, about 600 min, or about 720 min. In someembodiments, the extraction is performed for a time period ranging fromat least about 10 min, about 100 min, about 200 min, about 300 min,about 400 min, about 500 min, or about 600 min. In some embodiments, theextraction is performed for a time period ranging from at most about 100min, about 200 min, about 300 min, about 400 min, about 500 min, about600 min, or about 720 min.

In another embodiment, and more usually, the extraction is performed fora time period ranging from 30-240 minutes. In some embodiments, theextraction is performed for a time period ranging from about 30 min toabout 240 min. In some embodiments, the extraction is performed for atime period ranging from about 30 min to about 60 min, about 30 min toabout 90 min, about 30 min to about 120 min, about 30 min to about 150min, about 30 min to about 180 min, about 30 min to about 210 min, about30 min to about 240 min, about 60 min to about 90 min, about 60 min toabout 120 min, about 60 min to about 150 min, about 60 min to about 180min, about 60 min to about 210 min, about 60 min to about 240 min, about90 min to about 120 min, about 90 min to about 150 min, about 90 min toabout 180 min, about 90 min to about 210 min, about 90 min to about 240min, about 120 min to about 150 min, about 120 min to about 180 min,about 120 min to about 210 min, about 120 min to about 240 min, about150 min to about 180 min, about 150 min to about 210 min, about 150 minto about 240 min, about 180 min to about 210 min, about 180 min to about240 min, or about 210 min to about 240 min. In some embodiments, theextraction is performed for a time period ranging from about 30 min,about 60 min, about 90 min, about 120 min, about 150 min, about 180 min,about 210 min, or about 240 min. In some embodiments, the extraction isperformed for a time period ranging from at least about 30 min, about 60min, about 90 min, about 120 min, about 150 min, about 180 min, or about210 min. In some embodiments, the extraction is performed for a timeperiod ranging from at most about 60 min, about 90 min, about 120 min,about 150 min, about 180 min, about 210 min, or about 240 min.

In some embodiments, the extraction is performed at a pressure rangingfrom 7 to 20,000 psi (50 kPa-138 MPa). In some embodiments, theextraction is performed at a pressure ranging from about 7 psi (50 kPa)to about 2,000 psi (14 MPa). In some embodiments, the extraction isperformed at a pressure ranging from about 7 psi (50 kPa) to about 300psi (2 MPa), about 7 psi (50 kPa) to about 600 psi (4 MPa), about 7 psi(50 kPa) to about 900 psi (6 MPa), about 7 psi (50 kPa) to about 1,200psi (8 MPa), about 7 psi (50 kPa) to about 1,500 psi (10 MPa), about 7psi (50 kPa) to about 1,800 psi (12 MPa), about 7 psi (50 kPa) to about2,000 psi (14 MPa), about 300 psi (2 MPa) to about 600 psi (4 MPa),about 300 psi (2 MPa) to about 900 psi (6 MPa), about 300 psi (2 MPa) toabout 1,200 psi (8 MPa), about 300 psi (2 MPa) to about 1,500 psi (10MPa), about 300 psi (2 MPa) to about 1,800 psi (12 MPa), about 300 psi(2 MPa) to about 2,000 psi (14 MPa), about 600 psi (4 MPa) to about 900psi (6 MPa), about 600 psi (4 MPa) to about 1,200 psi (8 MPa), about 600psi (4 MPa) to about 1,500 psi (10 MPa), about 600 psi (4 MPa) to about1,800 psi (12 MPa), about 600 psi (4 MPa) to about 2,000 psi (14 MPa),about 900 psi (6 MPa) to about 1,200 psi (8 MPa), about 900 psi (6 MPa)to about 1,500 psi (10 MPa), about 900 psi (6 MPa) to about 1,800 psi(12 MPa), about 900 psi (6 MPa) to about 2,000 psi (14 MPa), about 1,200psi (8 MPa) to about 1,500 psi (10 MPa), about 1,200 psi (8 MPa) toabout 1,800 psi (12 MPa), about 1,200 psi (8 MPa) to about 2,000 psi (14MPa), about 1,500 psi (10 MPa) to about 1,800 psi (12 MPa), about 1,500psi (10 MPa) to about 2,000 psi (14 MPa), or about 1,800 psi (12 MPa) toabout 2,000 psi (14 MPa). In some embodiments, the extraction isperformed at a pressure ranging from about 7 psi (50 kPa), about 300 psi(2 MPa), about 600 psi (4 MPa), about 900 psi (6 MPa), about 1,200 psi(8 MPa), about 1,500 psi (10 MPa), about 1,800 psi (12 MPa), or about2,000 psi (14 MPa). In some embodiments, the extraction is performed ata pressure ranging from at least about 7 psi (50 kPa), about 300 psi (2MPa), about 600 psi (4 MPa), about 900 psi (6 MPa), about 1,200 psi (8MPa), about 1,500 psi (10 MPa), or about 1,800 psi (12 MPa). In someembodiments, the extraction is performed at a pressure ranging from atmost about 300 psi (2 MPa), about 600 psi (4 MPa), about 900 psi (6MPa), about 1,200 psi (8 MPa), about 1,500 psi (10 MPa), about 1,800 psi(12 MPa), or about 2,000 psi (14 MPa).

In yet another embodiment, the extraction is performed at a pressureranging from 10 to 20 psi (70-140 kPa). In some embodiments, theextraction is performed at a pressure ranging from about 10 psi (70 kPa)to about 20 psi (140 kPa). In some embodiments, the extraction isperformed at a pressure ranging from about 10 psi (70 kPa) to about 12psi (80 kPa), about 10 psi (70 kPa) to about 14 psi (100 kPa), about 10psi (70 kPa) to about 16 psi (110 kPa), about 10 psi (70 kPa) to about18 psi (120 kPa), about 10 psi (70 kPa) to about 20 psi (140 kPa), about12 psi (80 kPa) to about 14 psi (100 kPa), about 12 psi (80 kPa) toabout 16 psi (110 kPa), about 12 psi (80 kPa) to about 18 psi (120 kPa),about 12 psi (80 kPa) to about 20 psi (140 kPa), about 14 psi (100 kPa)to about 16 psi (110 kPa), about 14 psi (100 kPa) to about 18 psi (120kPa), about 14 psi (100 kPa) to about 20 psi (140 kPa), about 16 psi(110 kPa) to about 18 psi (120 kPa), about 16 psi (110 kPa) to about 20psi (140 kPa), or about 18 psi (120 kPa) to about 20 psi (140 kPa). Insome embodiments, the extraction is performed at a pressure ranging fromabout 10 psi (70 kPa), about 12 psi (80 kPa), about 14 psi (100 kPa),about 16 psi (110 kPa), about 18 psi (120 kPa), or about 20 psi (140kPa). In some embodiments, the extraction is performed at a pressureranging from at least about 10 psi (70 kPa), about 12 psi (80 kPa),about 14 psi (100 kPa), about 16 psi (110 kPa), or about 18 psi (120kPa). In some embodiments, the extraction is performed at a pressureranging from at most about 12 psi (80 kPa), about 14 psi (100 kPa),about 16 psi (110 Pa), about 18 psi (120 kPa), or about 20 psi (140kPa).

In some embodiments, the extraction is performed with a solvent to solidratio in the range 10 to 100 mL/g, wherein the solid is the driedpowdered biomass. In one embodiment, the extraction is performed with asolvent to solid ratio of 20 mL/g. In some embodiments, the extractionis performed with a solvent to solid ratio in the range of about 10 mL/gto about 100 mL/g. In some embodiments, the extraction is performed witha solvent to solid ratio in the range of about 10 mL/g to about 20 mL/g,about 10 mL/g to about 30 mL/g, about 10 mL/g to about 40 mL/g, about 10mL/g to about 50 mL/g, about 10 mL/g to about 60 mL/g, about 10 mL/g toabout 70 mL/g, about 10 mL/g to about 80 mL/g, about 10 mL/g to about 90mL/g, about 10 mL/g to about 100 mL/g, about 20 mL/g to about 30 mL/g,about 20 mL/g to about 40 mL/g, about 20 mL/g to about 50 mL/g, about 20mL/g to about 60 mL/g, about 20 mL/g to about 70 mL/g, about 20 mL/g toabout 80 mL/g, about 20 mL/g to about 90 mL/g, about 20 mL/g to about100 mL/g, about 30 mL/g to about 40 mL/g, about 30 mL/g to about 50mL/g, about 30 mL/g to about 60 mL/g, about 30 mL/g to about 70 mL/g,about 30 mL/g to about 80 mL/g, about 30 mL/g to about 90 mL/g, about 30mL/g to about 100 mL/g, about 40 mL/g to about 50 mL/g, about 40 mL/g toabout 60 mL/g, about 40 mL/g to about 70 mL/g, about 40 mL/g to about 80mL/g, about 40 mL/g to about 90 mL/g, about 40 mL/g to about 100 mL/g,about 50 mL/g to about 60 mL/g, about 50 mL/g to about 70 mL/g, about 50mL/g to about 80 mL/g, about 50 mL/g to about 90 mL/g, about 50 mL/g toabout 100 mL/g, about 60 mL/g to about 70 mL/g, about 60 mL/g to about80 mL/g, about 60 mL/g to about 90 mL/g, about 60 mL/g to about 100mL/g, about 70 mL/g to about 80 mL/g, about 70 mL/g to about 90 mL/g,about 70 mL/g to about 100 mL/g, about 80 mL/g to about 90 mL/g, about80 mL/g to about 100 mL/g, or about 90 mL/g to about 100 mL/g. In someembodiments, the extraction is performed with a solvent to solid ratioin the range of about 10 mL/g, about 20 mL/g, about 30 mL/g, about 40mL/g, about 50 mL/g, about 60 mL/g, about 70 mL/g, about 80 mL/g, about90 mL/g, or about 100 mL/g. In some embodiments, the extraction isperformed with a solvent to solid ratio in the range of at least about10 mL/g, about 20 mL/g, about 30 mL/g, about 40 mL/g, about 50 mL/g,about 60 mL/g, about 70 mL/g, about 80 mL/g, or about 90 mL/g. In someembodiments, the extraction is performed with a solvent to solid ratioin the range of at most about 20 mL/g, about 30 mL/g, about 40 mL/g,about 50 mL/g, about 60 mL/g, about 70 mL/g, about 80 mL/g, about 90mL/g, or about 100 m L/g.

Extraction Process 2

In some embodiments, referring to FIG. 15 , a process for extracting thepsychoactive alkaloid is shown. The psychoactive alkaloid source isdried in step 1500 by techniques known in the art, such as using aforced air oven.

In step 1510, the dried psychoactive alkaloid source or dried biomass ismixed with a solvent and/or left to soak. The solvent in which theextract is carried or dissolved may be a primary aliphatic alcohol, aketone, water, and any combination selected therefrom. In someembodiments, the primary aliphatic alcohol is a C1-4 alcohol. In someembodiments, the primary aliphatic alcohol is 5% ethanol. In someembodiments, the primary aliphatic alcohol is ethanol. In someembodiments, the ketone is a C3-4 ketone. In yet other embodiments, thewater is selected from deionized, distilled, reverse osmosis, orotherwise purified water, which is substantially without free ions. Inother embodiments, the water is not purified. In an exemplaryembodiment, the solvent is a hydro-ethanol mixture with 3 parts ofethanol to 1 part of water, by weight.

In step 1520, the mixture of the solvent and the dried psychoactivealkaloid source is filtered to obtain a filtrate and a filtrate residue.Some or all of the solvent is evaporated from the filtrate residue toobtain the psychoactive alkaloid extract. Standardization of theobtained psychoactive alkaloid extract is carried out according to thestandardization step 160 described above.

Optionally, the filtrate residue obtained in step 1520 is extracted withthe solvent again. The filtrate residue is extracted by repeating thesteps 1510 and 1520. This results in another filtrate. The firstfiltrate and the second filtrate are mixed together after theirrespective filtration steps to result in a bulk filtrate. The solventfrom this bulk filtrate is partially evaporated to obtain thepsychoactive alkaloid extract in a slurry form for the standardizationstep 160.

In one embodiment, the extraction is carried out at a temperatureranging from 5-95° C. The useful temperature range spans most of theliquid state of the solvent used, and upper and lower limits aredetermined by physical practicalities and limits of the availableapparatus. Still, the temperature of the solvent may be outside of thisrange in other embodiments.

In other embodiments, the extraction is carried out at a temperature of70° C. Temperature, and pressure if applied, are generally selected sothat the solvent does not boil if elevated temperatures are used. In oneembodiment, the extraction is carried out for a time duration rangingfrom 10 minutes to 12 hours. In yet another embodiment, the extractionis carried out for a time duration of 4 hours.

Extraction Process 3

In FIG. 10 , the extracting step 1000 may include, as an example,extracting psychoactive alkaloids from raw, psychedelic mushrooms. Themushrooms are dried and ground to result in a dried biomass. The nextstep involves heating the dried biomass in a solvent in order for theextraction to occur. The obtained slurry is filtered to obtain a firstfiltrate and a first residue. The first residue undergoes a secondextraction, using a second solvent to obtain a second slurry, which isthen filtered to obtain a second filtrate and a second residue. Thefirst filtrate and the second filtrate are mixed to obtain thepsychoactive alkaloid extract. More extract can be obtained this way,i.e., by splitting the solvent into two or more batches and using eachone sequentially to soak the biomass, compared to using a single volumeof solvent.

The extraction may further include completely or partially concentratingthe obtained psychoactive alkaloid extract, by evaporation of thesolvent from the combined filtrates.

In one embodiment, the first solvent and the second solvent are selectedfrom a primary aliphatic alcohol, a ketone, water, and any combinationtherefrom. In one embodiment, the primary aliphatic alcohol is a C1-4alcohol. In one embodiment, the ketone is a C3-4 ketone. In anotherembodiment, the first solvent is an ethanol-water mixture with 3 partsethanol to 1 part water by weight. In another embodiment, the secondsolvent is an ethanol-water mixture with 3 parts ethanol to 1 part waterby weight. In yet another embodiment, the water is selected fromdeionized, distilled, reverse osmosis, or otherwise purified water,which has substantially no free ions. The selection of the solvent willdepend on the nature of the starting material for extraction and thereaction conditions, according to which a person of skill in the art canmake the appropriate solvent selection.

In one embodiment, the extraction is carried out at a temperatureranging from 5-95° C. The useful temperature range spans most of theliquid state of the solvent used, and upper and lower limits aredetermined by physical practicalities and limits of the availableapparatus. Still, the temperature of the solvent may be outside of thisrange in other embodiments.

In another embodiment, the extraction is carried out at a temperature of70° C. Temperature and pressure, if applied, are generally selected sothat the solvent does not boil if elevated temperatures are used. In oneembodiment, the extraction is carried out for a time duration rangingfrom 10 minutes to 12 hours. In yet another embodiment, the extractionis carried out for a time duration of 4 hours.

Extraction Process 4

In one embodiment, referring to FIG. 18 , a basic process for obtaininga psychoactive alkaloid extract with a desired amount of aphosphorylated psychoactive alkaloid and a desired amount of adephosphorylated psychoactive alkaloid is shown. The phosphorylatedalkaloid may be psilocybin, baeocystin, norbaeocystin, aeruginascin, orany combination selected therefrom. The dephosphorylated alkaloid may bepsilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination selectedtherefrom. The control aspect of the present invention relates topsychoactive alkaloids that have phosphorylated forms and not to otherpsychoactive alkaloids that may be present in a psychoactive alkaloidsource. Depending on the strain or harvest, there may be no orsubstantially no phosphorylatable psychoactive alkaloids in thepsychoactive alkaloid source, or they may represent as much 80-90% ofthe total alkaloid content.

The process includes step 1800 of obtaining powdered biomass from apsychoactive alkaloid source. The powdered biomass is obtained by dryingand pulverizing a psychoactive alkaloid source. The drying is carriedout via vacuum desiccation, freeze drying, timed forced air drying, orother existing drying method, to obtain a dried biomass. Thepulverization is carried out by milling, grinding, or other method toreduce the particle size of the dried biomass. In one embodiment, thedrying is carried out in a forced air oven completely shielded from alllight at 20-30° C. for a time period of 5-10 hours. However, there isroom for optimization of the drying step, using different temperatures(e.g., 10-50° C.) and different durations.

In one embodiment, the drying is carried out in a manner to not promotethe conversion of phosphorylated psychoactive alkaloid. Taking care notto bruise while harvesting the psychoactive alkaloid source, harvestingat the right time of the fruiting body life cycle, potentiallyfreeze-drying the fruiting body, low heat desiccation, and gentle airdrying are all ways that reduce the conversion of phosphorylatedpsychoactive alkaloid to dephosphorylated psychoactive alkaloid. It maybe feasible to harvest the fungi in a basic or methanol environment orsoak the whole mycelium in methanol and cut the fruits while soaked.Once dried, there is negligible conversion, so that subsequentpulverization has little effect on it, unless moisture is added back.The prevention of conversion of phosphorylated psychoactive alkaloid todephosphorylated psychoactive alkaloid during harvesting allows for thepreparation of psychoactive alkaloid extracts, by the present process,having a total phosphorylatable psychoactive alkaloid content that is upto 100% by weight of phosphorylated psychoactive alkaloid.

Step 1810 involves extracting a psychoactive alkaloid from the driedpowdered biomass with an acidified solvent or a basified solvent toobtain a psychoactive alkaloid liquid with a specific pH, wherein thespecific pH is lower than 3.5 or greater than 10.5. Between pH 3.5 andpH 10.5, the conditions are such that psilocybin is readily converted topsilocin, and psilocin is converted to the quinoid dimer, which iscompletely inactive.

When used, the acid may be acetic acid, adipic acid, ascorbic acid,phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic,ammonium citrate monobasic, calcium citrate, calcium fumarate, calciumgluconate, calcium phosphate dibasic, calcium phosphate monobasic,hydrochloric acid, sulfuric acid monobasic, calcium phosphate tribasic,citric acid, fumaric acid, gluconic acid, magnesium fumarate, malicacid, phosphoric acid, potassium acid tartrate, potassium citrate,potassium fumarate, sodium citrate, sodium fumarate, sodium gluconate,sodium lactate, sodium potassium hexametaphosphate, sodium potassiumtartrate, sodium potassium tripolyphosphate, sodium pyrophosphatetetrabasic, sodium tripolyphosphate, tartaric acid, and any combinationof one or more of these. In some embodiments, the acid is either onlyhydrochloric acid or only phosphoric acid, for example. It is alsoenvisaged that other acids may be used, for example, non-food-gradeacids that may be used by pharmaceuticals.

When used, the base may be ammonium bicarbonate, ammonium carbonate,ammonium hydroxide, calcium acetate, calcium carbonate, calciumchloride, calcium hydroxide, calcium lactate, calcium oxide, calciumphosphate dibasic, calcium phosphate monobasic, magnesium carbonate,potassium aluminum sulphate, potassium bicarbonate, potassium carbonate,potassium hydroxide, potassium lactate, potassium phosphate dibasic,potassium pyrophosphate tetrabasic, potassium phosphate tribasic,potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate,sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate,sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, or any combination therefrom. Inone embodiment, the base is solely sodium hydroxide, for example. Otherbases may be used in other embodiments, for example, non-food-gradebases that may be used by pharmaceuticals.

After adding the acidified solvent or the basified solvent, thepsychoactive alkaloid liquid has a pH ranging from 0.5 to 3.5 or from10.5 to 13.5, respectively. In an exemplary embodiment, the pH of thepsychoactive alkaloid liquid obtained after addition of the basifiedsolvent is 13. In another exemplary embodiment, the pH of thepsychoactive alkaloid liquid obtained after addition of the acidifiedsolvent is 2.

The pH is adjusted in the extraction step 1810 to halt or promoteconversion of phosphorylated psychoactive alkaloid to dephosphorylatedpsychoactive alkaloid, thus allowing the preparation of the psychoactivealkaloid liquid with the desired amount of a phosphorylated psychoactivealkaloid and a desired amount of a dephosphorylated psychoactivealkaloid. A specific pH lower than 3.5 promotes the conversion of thephosphorylated psychoactive alkaloid to the dephosphorylatedpsychoactive alkaloid. A specific pH greater than 10.5 halts theconversion of the phosphorylated psychoactive alkaloid to thedephosphorylated psychoactive alkaloid.

In step 1820 of the process, the pH of the obtained psychoactivealkaloid liquid is adjusted to a pH ranging from 3.5 to 4.5. The pH isadjusted by adding a base or an acid. The pH is adjusted to a value inthis range as the psychoactive alkaloid liquid exhibits a goodanti-microbial stability in this pH range. Also, there is nodephosphorylation at this pH after the alkaloids are removed from thebiomass, which points to enzymatic hydrolysis being responsible forconversion in the source of the psychoactive alkaloids. In exemplaryembodiments, the base is sodium hydroxide, and the acid is citric acid.Any other appropriate acid or base can be used to adjust the pH, which aperson of skill in the art may determine. The selection of the acid orthe base will depend upon the nature of the pH of the psychoactivealkaloid liquid prior to adjusting it to the range of 3.5-4.5, accordingto which a person of skill in the art can make the appropriate acid orbase selection.

Step 1830 of the process involves evaporating the solvent from thepsychoactive alkaloid solution to obtain the psychoactive alkaloidextract with the desired amount of the phosphorylated psychoactivealkaloid and the desired amount of the dephosphorylated psychoactivealkaloid. The solvent is completely or partially evaporated to result inthe psychoactive alkaloid extract (slurry or powder) with the desiredamount of the phosphorylated psychoactive alkaloid and the desiredamount of the dephosphorylated psychoactive alkaloid. The evaporation iscarried out by methods such as air drying, rotary evaporation, or otherexisting methods to evaporate solvent from psychoactive alkaloid liquid.At this point in time, away from the biomass, psilocybin and/or psilocinare fairly heat resistant, more so under vacuum, thus, rotaryevaporation, for example, is a suitable process. The desired amount ofthe phosphorylated psychoactive alkaloid is 0-100% of a phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Thedesired amount of the dephosphorylated psychoactive alkaloid is theremainder of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract.

In some embodiments, when the psychoactive alkaloid liquid has a pHgreater than 10.5 during the extraction step, the desired amount of thephosphorylated psychoactive alkaloid is 50-90% by weight (crudeextraction) of the total phosphorylatable psychoactive alkaloid contentin the psychoactive alkaloid extract, without going to onerous lengthsin selecting the raw material. The desired amount of thedephosphorylated psychoactive alkaloid is the remainder of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract.

In another embodiment, when using a psychoactive alkaloid source thathas not undergone conversion (i.e. no significant conversion) of anyphosphorylated alkaloid to dephosphorylated alkaloid, and when thepsychoactive alkaloid liquid has a pH greater than 10.5 during theextraction step, the desired amount of the phosphorylated psychoactivealkaloid is 100% by weight of the total phosphorylatable psychoactivealkaloid content in the psychoactive alkaloid extract. The desiredamount of the dephosphorylated psychoactive alkaloid is 0% by weight ofthe total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid extract.

In yet another embodiment, when the psychoactive alkaloid liquid has apH lower than 3.5 during the extraction step, the desired amount of thephosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract. The desired amount of the dephosphorylatedpsychoactive alkaloid is 100% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Evenwith neutral hydro-ethanol extraction, a large portion of psilocybin maybe converted to psilocin. However, the low pH environment (<3.5)protects the psilocin from oxidation.

Extraction Process 5

In some embodiments, referring to FIG. 19 , additional, optional stepsin the extraction step 1810 are shown. Step 1900 is performed by addingthe acidified solvent or the basified solvent to the powered biomass.The obtained psychoactive liquid has a specific pH, the specific pHbeing lower than 3.5 or greater than 10.5. After the addition of theacidified solvent or the basified solvent, the powered biomass and thesolvent are mixed, followed by step 1910 of filtration to result in theextracted filtrate of step 1920 (i.e. psychoactive alkaloid liquid). Tothis obtained filtrate, the acid or the base of step 1820 is added toadjust the pH to within the range of 3.5-4.5.

In some embodiments, the extraction step comprises further extractingthe psychoactive alkaloid by repeating the extraction step. Filtrateresidue from step 1910 is collected, and to this filtrate residue, thesame or a different acidified solvent or the same or a differentbasified solvent is added. The resulting mixture is mixed followed byfiltration to obtain another filtrate. This filtrate and the previousfiltrate are mixed together to result in a bulk filtrate. To this bulkfiltrate the acid or the base is added to adjust the pH to 3.5-4.5according to step 1820.

In some embodiments, further extraction of the filtrate obtained afterextraction with the acidified or the basified solvent is repeated untila required amount of the phosphorylated psychoactive alkaloid and/or thedephosphorylated psychoactive alkaloid is extracted. The number ofextraction cycles to be repeated may depend on various variable factorssuch as the source of the psychoactive alkaloid and the solubility ofthe psychoactive alkaloid in the acidified or the basified solvent.

The solvent in the evaporation step can be completely or partiallyevaporated, to result in a powdered solid or a slurry. Evaporation maybe paused, for standardization, and continued after.

Extraction Process 6

Referring to FIG. 20 , the present invention also relates to a processfor obtaining a psychoactive alkaloid composition with a psychoactivealkaloid extract and one or more excipients.

At step 2000 the evaporation step 1830 (FIG. 18 ) is paused when aportion of the solvent has been evaporated from the psychoactivealkaloid liquid to obtain a psychoactive alkaloid slurry. Theevaporation of a portion of the solvent, before collection of thepsychoactive alkaloid slurry for standardization, is done to obtain aquantity of a psychoactive alkaloid slurry that is easy to handle in thesubsequent steps of the standardization process. The quantity of theportion of the solvent to be evaporated before pausing the evaporationis not so much as to make it too viscous to handle well. The quantity ofthe portion of the solvent to be evaporated will depend on variousfactors, for example, but not limited to, the contents of thepsychoactive alkaloid liquid and the quantity of the psychoactivealkaloid liquid present at the beginning of the evaporation step.

Step 2010 includes standardizing the obtained psychoactive alkaloidslurry by adding thereto a measured quantity of one or more excipientsto obtain a standardized slurry with a specific amount of psychoactivealkaloid content. The specified amount of the total psychoactivealkaloid content in the psychoactive alkaloid composition is achieved byfirst determining the proportion, by weight, of solids in thepsychoactive alkaloid slurry. The weight proportion of the psychoactivealkaloids in the slurry is also determined. Then, a measured amount ofone or more excipients is added to a measured amount of the psychoactivealkaloid slurry. Thus, after evaporation of the remaining solvent, theresultant composition is a standardized composition with a specifiedtotal psychoactive alkaloid content.

Step 2020 includes continuing the evaporating step 1830 (FIG. 18 ) bydrying the standardized slurry to obtain a psychoactive alkaloidcomposition with the psychoactive alkaloid extract and the one or moreexcipients.

The evaporation in the standardization process is carried out by methodssuch as air drying, rotary evaporation, or other methods known in theart to suitably evaporate solvent from psychoactive alkaloid slurry.

The psychoactive alkaloid composition obtained has a specific totalpsychoactive alkaloid content in the composition due to thestandardizing step. The specified amount of the total psychoactivealkaloid content may be accurate to one or two decimal places, or one ortwo significant figures depending on how accurately the measurements aremade during the standardization process.

Thus, the psychoactive alkaloid composition obtained has a specificamount of a total psychoactive alkaloid content, which is made up of adesired amount of phosphorylated psychoactive alkaloid and a desiredamount of dephosphorylated psychoactive alkaloid, and possibly otherpsychoactive alkaloids that are not phosphorylatable.

In one embodiment, the specific amount of the total psychoactivealkaloid content in the psychoactive alkaloid composition ranges from0.1-99% by weight of the composition, the higher concentrations beingobtained when purifying steps are included. Purifying may involvetreating the extract with a resinous material prior to thestandardization step, to remove impurities such as sugars and proteins.In another embodiment, the specific amount of the total psychoactivealkaloid content in the psychoactive alkaloid composition ranges from0.1-10% by weight of the composition, which may be achieved withoutpurifying steps. In an exemplary embodiment, the specific amount of thetotal psychoactive alkaloid content in the psychoactive alkaloidcomposition is 0.53% by weight of the composition. In yet anotherexemplary embodiment, the specific amount of the total psychoactivealkaloid content in the psychoactive alkaloid composition is 0.501% byweight of the composition.

In some embodiments, the desired amount of the phosphorylatedpsychoactive alkaloid is 0-100% by weight of a total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract, andthe desired amount of the dephosphorylated psychoactive alkaloid is theremainder of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract. In one embodiment, the desired amountof the phosphorylated psychoactive alkaloid is 10-90% by weight of thetotal phosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is the remainder of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract. Inanother embodiment, the desired amount of the phosphorylatedpsychoactive alkaloid is 0% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract, andthe desired amount of the dephosphorylated psychoactive alkaloid is 100%by weight of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract. In yet another embodiment, thedesired amount of the phosphorylated psychoactive alkaloid is 100% byweight of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract, and the desired amount of thedephosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract.

Further Processes

Referring to FIG. 10 additional, optional steps are shown well as thebasic steps in the process. In one embodiment, the extraction step 1000is followed by completely or partially concentrating the obtainedpsychoactive alkaloid extract (or solution) by evaporation of thesolvent from the extract in step 1010. In other embodiments, step 1010of partially or completely evaporating the solvent may be considered tobe a part of the extraction step 1000. If the solvent from the extracthas been completely evaporated in step 1010, then reverse osmosis water,more solvent, or another solvent is added back.

In some embodiments, the process includes adding, in step 1020, an acidor a base to the psychoactive alkaloid extract obtained in step 1000 toobtain a psychoactive alkaloid solution with a specific pH.

When used, the acid may be acetic acid, adipic acid, ascorbic acid,phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic,ammonium citrate monobasic, calcium citrate, calcium fumarate, calciumgluconate, calcium phosphate dibasic, calcium phosphate monobasic,hydrochloric acid, sulfuric acid monobasic, calcium phosphate tribasic,citric acid, fumaric acid, gluconic acid, magnesium fumarate, malicacid, phosphoric acid, potassium acid tartrate, potassium citrate,potassium fumarate, sodium citrate, sodium fumarate, sodium gluconate,sodium lactate, sodium potassium hexametaphosphate, sodium potassiumtartrate, sodium potassium tripolyphosphate, sodium pyrophosphatetetrabasic, sodium tripolyphosphate, tartaric acid, and any combinationof one or more of these. In some embodiments, the acid is either onlyhydrochloric acid or only phosphoric acid, for example. It is alsoenvisaged that other acids may be used.

When used, the base may be ammonium bicarbonate, ammonium carbonate,ammonium hydroxide, calcium acetate, calcium carbonate, calciumchloride, calcium hydroxide, calcium lactate, calcium oxide, calciumphosphate dibasic, calcium phosphate monobasic, magnesium carbonate,potassium aluminum sulphate, potassium bicarbonate, potassium carbonate,potassium hydroxide, potassium lactate, potassium phosphate dibasic,potassium pyrophosphate tetrabasic, potassium phosphate tribasic,potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate,sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate,sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, or any combination therefrom. Inone embodiment, the base is solely sodium hydroxide, for example. Otherbases may be used in other embodiments.

In one embodiment, the specific pH psychoactive alkaloid solution has apH ranging from 2.5 to 4.5, or from 9 to 10. In other embodiments, thespecific pH psychoactive alkaloid solution has a pH of 3, 4, or 9.5. Theselection of the pH is chosen in a manner to allow for the efficientadsorption of the psychoactive alkaloids onto the resin(s).

In one embodiment, the process includes adding phosphoric acid to thepsychoactive alkaloid extract to achieve a pH of 4. In anotherembodiment, the process includes adding hydrochloric acid to thepsychoactive alkaloid extract to achieve a pH of 3. In yet anotherembodiment, the process includes adding sodium hydroxide to thepsychoactive alkaloid extract to achieve a pH of 9.5.

The process includes, in step 1030, optionally filtering, centrifuging,or clarifying the psychoactive alkaloid solution or specific pHpsychoactive alkaloid solution, as the case may be, and utilizing theobtained filtrate for the next step 1040 of adsorption. Clarifying maybe performed, for example, by adding an agglomeration agent.

In step 1040, the process involves adsorbing the psychoactivealkaloid(s) in the solution onto the resin to obtain an adsorbedpsychoactive alkaloid.

In step 1050, the process involves washing the resin to remove adsorbedimpurities from the resin. While not all the impurities are adsorbedonto the resin, some of them may be. The washing step, substantially,does not remove the adsorbed psychoactive alkaloids. The washing solventmay be 100% ethanol, 100% reverse osmosis water, or any other washingsolvent used in ion-exchange resin chromatography, provided that thewashing removes impurities or by-products that are adsorbed on theresin. Impurities or by-products may include, for example, sugars,carbohydrates, chitin, chitosan, fats, minerals, waxes, or proteins.There may be one, two, or more washing steps depending on theembodiment, and the same or different washing solvents may be used foreach wash. In other embodiments, the solvent(s) for washing may includea primary aliphatic alcohol, a ketone, water, and any combinationtherefrom. In one embodiment, the primary aliphatic alcohol is a C1-4alcohol. In one embodiment, the primary aliphatic alcohol is 5% ethanol.In one embodiment, the primary aliphatic alcohol is ethanol. In oneembodiment, the ketone is a C3-4 ketone. In yet another embodiment, thewater is selected from deionized, distilled, reverse osmosis, orotherwise purified water that is substantially without free ions.

After the washing, the process involves eluting, in step 1060, theadsorbed psychoactive alkaloid from the resin using a solvent to obtaina purified psychoactive alkaloid solution. The solvent may be an organicsolvent, an acid, a base, or water, a combination of an organic solventand a base, or a combination of an organic solvent and an acid, acombination of an organic solvent and water, a combination of water anda base, or combination of water and an acid. The result of the elutionstep is a purified psychoactive alkaloid solution.

Following the elution, a further washing step 1070 may be employed using100% ethanol, for example, to wash the resin. This may be considered tobe a cleaning step, to refresh the resin and make it ready to be usedagain in a subsequent step or in another process. In other embodiments,the solvent for further washing may be a primary aliphatic alcohol, aketone, water, and any combination therefrom. In one embodiment, theprimary aliphatic alcohol is a C1-4 alcohol. In one embodiment, theprimary aliphatic alcohol is 5% ethanol. In one embodiment, the ketoneis a C3-4 ketone. In yet another embodiment, the water is selected fromdeionized, distilled, reverse osmosis, or otherwise purified water thatis substantially without free ions.

The result of the elution is a purified psychoactive alkaloid solution.In one embodiment, the purified psychoactive alkaloid solution has aconcentration of 0.07% by weight of a psychoactive alkaloid, which isthe concentration before removal of some or all of the solvent. Thisconcentration may be different in other embodiments, depending on theamount solvent used for the elution and the potency of the rawmaterials. In one embodiment, the purified psychoactive alkaloidsolution is concentrated by evaporating the solvent to form a purifiedpsychoactive slurry that has at least of 5% by weight or more of apsychoactive alkaloid. In another embodiment, the purified psychoactivealkaloid slurry has 5-68% by weight of a psychoactive alkaloid. In yetother embodiments, the purified psychoactive alkaloid slurry has aconcentration of psychoactive alkaloid outside these ranges, and, whendried, can be as low as 0.1% or as high as 99% dry wt/wt %.

Optionally, the obtained purified psychoactive alkaloid solution isfurther purified by filtering the obtained purified psychoactivealkaloid solution to obtain a filtrate, and then repeating at leaststeps 1040 and 1060 with the obtained filtrate.

Different processes may employ the steps in a different order, and someof the steps may be repeated with the same or different parameters. Forexample, in one embodiment, starting from a solution of dissolvedextract, the order of the steps may be 1020, 1040, 1030, 1050, 1060,1020, 1030, 1010, 1030, 1040, 1050 and 1060.

Variations

Other water may be used in place of reverse osmosis water, which may beselected for its purity.

Water purified by other purification technologies may be used instead ofreverse osmosis water. In alternative embodiments, the solvent is 0.02%to 1.5% acetic acid in water. In alternate embodiment, the solventcomprises 75% ethanol, 25% water, and 0.1M sodium hydroxide. Inalternative embodiments the solvent is a hydro-methanol mixture, with amethanol content in the range of below 1% to 100%. The hydro-methanolbased extraction follows the same steps as the extraction with a mixtureof ethanol and water (FIG. 3 ) and may use lower soaking temperaturesdue to the lower boiling point of methanol. Also, the methanol/watermixture can be evaporated to dryness instead of the partial evaporationin step 360, for safety. If evaporated to dryness, the extract is thenformed by adding to the residual solid. If not evaporated to dryness,the residual slurry is diluted, if necessary for ease of handling, byadding reverse osmosis water to form the slurry. If not diluted, theresidual slurry is used as the concentrated slurry. The result ofevaporating the methanol is a residue that is either solid or a slurry.Furthermore, the hydro-methanol solvent may be buffered with a strongacid or a strong alkali, following the processes in FIGS. 6 and 7 .Again, however, the solvent may be completely evaporated instead ofpartially (612, 712) in order to fully remove the methanol, with reverseosmosis water being added to the solid to form the concentrated slurry.If the solvent is not completely evaporated, it should be evaporatedenough to remove all the methanol and leave a residual slurry. Theresidual slurry may optionally then be diluted, for ease of handling,with reverse osmosis water to form the concentrated slurry. If notdiluted, the residual slurry is used as the concentrated slurry.

The solvent may also be propan-1-ol, propan-2-ol, a butanol isomer, or amixture of any or all of these with water, in any percentage ratio.

Any of the solvents described herein may be used with any of themushroom varieties that include psychoactive alkaloids.

The temperature of extraction may be lowered to reduce conversion, andthe duration may be in the range of 30 to 240 minutes.

In other embodiments, other drying techniques, temperatures anddurations may be used. It is possible in other embodiments to grind thedried biomass to lower or higher particle size than 200 mesh. Forexample, grinding to a mesh size of 40 would work in some embodiments.The choice of solvent may have an impact on which mesh size to grind thedried mushrooms to. Note that, in other embodiments, the grinding step614 may take place before or after the drying step 613.

In general, unless otherwise indicated, singular elements may be in theplural and vice versa with no loss of generality.

Temperatures that have been given to the nearest degree include alltemperatures within a range of ±0.5° C. of the given value. Likewise,numbers and percentages are specified to the nearest significant digit.Values of pH are specified to ±0.5.

While exemplary pH ranges are given in some examples, other pH rangesare possible.

The process may be scaled up using larger quantities and modifiedapparatus.

The extraction process in other embodiments may use varying appliedpressures and temperatures, which vary during the soaking steps.

Chemical and physical stability may be determined using rigorousstability testing protocols. This would be a necessary study for theproduct to be considered made using a good manufacturing process. Theinitial specifications and ongoing specifications of the extract shouldbe determined during a testing regime over time, temperature, relativehumidity, etc. to determine the physical and chemical stability. Studiesare on-going, but a 5-year shelf life with a minimum of 2 years istargeted in terms of physical and chemical stability.

E. Purification

Purification Process 1

In one embodiment, referring to FIG. 9 , a basic process for obtaining apurified psychoactive alkaloid solution from extracted psychoactivecompounds is shown. The process includes the step 900 of extracting apsychoactive alkaloid from a psychoactive alkaloid source to obtain apsychoactive alkaloid extract. The psychoactive alkaloid source may be afungus, a mycelium, an animal, a spore, a plant, a bacterium, or ayeast. The psychoactive alkaloid source in some embodiments may be aprior extract of one or more psychoactive alkaloids, where the priorextract is to undergo a further extraction/purification process. Thepsychoactive alkaloid may include, but is not limited to, psilocybin,psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin,bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine),N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine,muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH),elymoclavine, ergometrinine, and/or chanoclavine. or any combinationtherefrom. The extract from the psychoactive alkaloid source may be afluid, as either a liquid or a slurry, or is made into a fluid by theaddition of a solvent.

The solvent in which the extract is carried or dissolved may be aprimary aliphatic alcohol, a ketone, water, and any combinationtherefrom. In one embodiment, the primary aliphatic alcohol is a C1-4alcohol. In one embodiment, the primary aliphatic alcohol is 5% ethanol.In one embodiment, the primary aliphatic alcohol is ethanol. In oneembodiment, the ketone is a C3-4 ketone. In yet another embodiment, thewater is selected from deionized, distilled, reverse osmosis, orotherwise purified water, which is substantially without free ions. Inother embodiments, the water is not purified.

The process then involves adsorbing, in step 910, the psychoactivealkaloid(s) in the extract obtained in step 900 onto a resin to obtainan adsorbed psychoactive alkaloid, which may include one or moreadsorbed psychoactive alkaloids.

In one embodiment, the resin is an adsorbent resin of the macroporoustype, such as, a cation or anion ion-exchange resin, a non-ionic resin,or any combination therefrom. Representative pharmaceutical,nutraceutical or food-grade grade resins for use in accordance with thepresent invention are known to those skilled in the art. For example,pharmaceutical grade non-ionic macroporous resins are commerciallyavailable, e.g. Amberlite® XAD4. In one embodiment, the resin is acationic ion-exchange resin or an anionic-exchange resin. The cationicion-exchange resin may be selected from commercially available cationicion-exchange resins known in the art, including, but not limited to,Amberlite® MAC-3 H. The cationic ion-exchange resin may be in an H⁺ formor an Na⁺ form. The anionic ion-exchange resin may be selected fromcommercially available anion exchange resins known in the art,including, but not limited to, Amberchrom® 50WX8. The anionicion-exchange resin may be in an OH⁻ form or a Cl⁻ form. The resins usedmay be of any particle size. In some embodiments, the resins may be geltype resins, with any size of gel bead.

Next, the process involves eluting, in step 920, the adsorbedpsychoactive alkaloid using a solvent to obtain a purified psychoactivealkaloid solution. The solvent may be, for example, an organic solvent,an acid, a base, a combination of an organic solvent and a base, acombination an organic solvent and an acid, water, a combination ofwater and acid, a combination of water and base, or a combination ofwater and an organic solvent. Usually, the solvent is different from thesolvent in which the extract is initially provided and is either adifferent type of solvent or a different composition of solvent. It maybe at a different temperature than the initial solvent.

In some embodiments, the solvent used in the elution step 920 may be aprimary aliphatic alcohol, a ketone, water, and any combinationtherefrom. In one embodiment, the primary aliphatic alcohol is a C1-4alcohol. In one embodiment, the primary aliphatic alcohol is 5% ethanol.In one embodiment, the primary aliphatic alcohol is ethanol. In oneembodiment, the ketone is a C3-4 ketone. In yet another embodiment, thewater is deionized, distilled, reverse osmosis, or otherwise purifiedwater, which is substantially without free ions. In other embodiments,the water is not purified.

In one embodiment, the solvent used in the elution step 920 is acombination of an organic solvent and an acid. In one embodiment, thecombination of an acid and an organic solvent is 2% hydrochloric acidand 80% ethanol, for example. In general, any acidic environment willdisplace some of the ions from the resin, but the rate and optimizationof the desorption will be affected by the acid concentration. In oneembodiment, the solvent used in the elution step 920 is a combination ofan organic solvent and a base. In one embodiment, the combination of anorganic solvent and a base is of 2% sodium chloride and 80% ethanol, forexample. In general, any basic environment will displace some of theions from the resin, but the rate and optimization of the desorptionwill be affected by the concentration of the base.

All the above solvents and combinations thereof are suitable for theelution step because all of the psychoactive alkaloids of interest aresoluble therein and, depending on the choice of resin, they are allcapable of pulling the alkaloids of interest off a resin. There are manydifferent resins available, and it is a straightforward matter to selecta suitable resin and elution solvent pair.

In one embodiment, the elution step is carried out at a temperature inthe range of 4-75° C. These temperatures are limited by the boilingpoint of the solvent used, as well as the specifications of allowablefood-grade resins, as determined by the manufacturers of the resins andgovernmental food and drug administrations. In another embodiment, theelution step is carried out at room temperature for convenience, i.e.,at 21-25° C.

In other embodiments, the process for obtaining the purifiedpsychoactive alkaloid solution further includes repeating the steps 910and 920 with the obtained purified psychoactive alkaloid solution toobtain a further or twice purified psychoactive alkaloid solution. Forthe repeated steps in these embodiments, the resin may be the same or adifferent resin, and the solvent may be the same or a different solvent.While the purified psychoactive alkaloid solution may have a lowpsychoactive alkaloid content, this may be increased by evaporation ofsome or all of the solvent.

Purification Process 2

In some embodiments, referring to FIG. 16 , a process for purifying thepsychoactive alkaloid extract obtained in step 1410 (FIG. 14 ) or step1520 (FIG. 15 ) is shown.

The process includes adding, in step 1600, an acid or a base to thepsychoactive alkaloid extract previously obtained, to result in aspecific pH psychoactive alkaloid solution.

When used, the acid may be acetic acid, adipic acid, ascorbic acid,phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic,ammonium citrate monobasic, calcium citrate, calcium fumarate, calciumgluconate, calcium phosphate dibasic, calcium phosphate monobasic,hydrochloric acid, sulfuric acid monobasic, calcium phosphate tribasic,citric acid, fumaric acid, gluconic acid, magnesium fumarate, malicacid, phosphoric acid, potassium acid tartrate, potassium citrate,potassium fumarate, sodium citrate, sodium fumarate, sodium gluconate,sodium lactate, sodium potassium hexametaphosphate, sodium potassiumtartrate, sodium potassium tripolyphosphate, sodium pyrophosphatetetrabasic, sodium tripolyphosphate, tartaric acid, or any combinationof one or more of these. In some embodiments, the acid is either onlyhydrochloric acid or only phosphoric acid, for example. It is alsoenvisaged that other acids may be used.

When used, the base may be ammonium bicarbonate, ammonium carbonate,ammonium hydroxide, calcium acetate, calcium carbonate, calciumchloride, calcium hydroxide, calcium lactate, calcium oxide, calciumphosphate dibasic, calcium phosphate monobasic, magnesium carbonate,potassium aluminum sulphate, potassium bicarbonate, potassium carbonate,potassium hydroxide, potassium lactate, potassium phosphate dibasic,potassium pyrophosphate tetrabasic, potassium phosphate tribasic,potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate,sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate,sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, or any combination selectedtherefrom. In one embodiment, the base is solely sodium hydroxide, forexample. Other bases may be used in other embodiments.

In some embodiments, the specific pH psychoactive alkaloid solution hasa pH ranging from 2.5 to 4.5 or from 9 to 10. In other embodiments, thespecific pH psychoactive alkaloid solution has a pH of 3, 4, or 9.5. Theselection of the pH is chosen in a manner to allow for the efficientadsorption of the psychoactive alkaloids onto the resin(s).

The process optionally includes partially evaporating the solvent fromthe specific pH psychoactive alkaloid solution.

The process optionally includes filtering, centrifuging, or clarifyingthe psychoactive alkaloid solution or specific pH psychoactive alkaloidsolution, as the case may be, and utilizing the obtained filtrate forthe next step 1610 of adsorption. Clarifying may be performed, forexample, by adding an agglomeration agent.

In step 1610, the process involves adsorbing the psychoactivealkaloid(s) in the specific pH psychoactive alkaloid solution onto aresin to obtain an adsorbed psychoactive alkaloid.

In step 1620, the process involves washing the resin to remove adsorbedimpurities from the resin. While not all the impurities are adsorbedonto the resin, some of them may be. The washing step, substantially,does not remove the adsorbed psychoactive alkaloids. The washing solventmay be 100% ethanol, 100% reverse osmosis water, or any other washingsolvent used in ion-exchange resin chromatography, provided that thewashing removes impurities or by-products that are adsorbed on theresin. Impurities or by-products may include, for example, sugars,carbohydrates, chitin, chitosan, fats, minerals, waxes, or proteins.There may be one, two or more washing steps depending on the embodiment,and the same or different washing solvents may be used for each wash.

In other embodiments, the solvent(s) for washing may include a primaryaliphatic alcohol, a ketone, water, and any combination selectedtherefrom. In some embodiments, the primary aliphatic alcohol is a C1-4alcohol. In some embodiments, the primary aliphatic alcohol is 5%ethanol. In some embodiments, the primary aliphatic alcohol is ethanol.In some embodiments, the ketone is a C3-4 ketone. In yet otherembodiments, the water is selected from deionized, distilled, reverseosmosis, or otherwise purified water that is substantially without freeions.

After the washing, the process involves eluting, in step 1630, theadsorbed psychoactive alkaloid from the resin using a solvent to obtaina purified psychoactive alkaloid extract. The solvent may be an organicsolvent, an acid, a base, or water, a combination of an organic solventand a base, or a combination of an organic solvent and an acid, acombination of an organic solvent and water, a combination of water anda base, or combination of water and an acid. The solvent from thepurified psychoactive alkaloid extract is partially evaporated to obtainthe purified psychoactive alkaloid extract in a slurry form for thestandardization step 1420.

In some embodiments, the solvent used in the elution step 1630 may be aC1-4 alcohol, a C3-4 ketone, water, and any combination selectedtherefrom. In one embodiment, the primary aliphatic alcohol is 5%ethanol. In yet another embodiment, the water is deionized, distilled,reverse osmosis, or otherwise purified water, which is substantiallywithout free ions. In one embodiment, the solvent used in the elutionstep 14 is a combination of an organic solvent and an acid. In general,any acidic environment will displace some of the ions from the resin,but the rate and optimization of the desorption will be affected by theacid concentration. In one embodiment, the solvent used is a combinationof an organic solvent and a base. In general, any basic environment willdisplace some of the ions from the resin, but the rate and optimizationof the desorption will be affected by the concentration of the base.

All the above solvents and combinations thereof are suitable for theelution step because all of the psychoactive alkaloids of interest aresoluble therein and, depending on the choice of resin, they are allcapable of pulling the alkaloids of interest off a resin. There are manydifferent resins available, and it is a straightforward matter to selecta suitable resin and elution solvent pair.

In one embodiment, the elution step is carried out at a temperature inthe range of 4-75° C. These temperatures are limited by the boilingpoint of the solvent used, as well as the specifications of allowablefood-grade resins, as determined by the manufacturers of the resins andgovernmental food and drug administrations. In another embodiment, theelution step is carried out at room temperature for convenience, i.e.,at 21-25° C.

In other embodiments, the process for obtaining the purifiedpsychoactive alkaloid

The extraction step further includes repeating the steps 1600 to 1630with the purified psychoactive alkaloid extract obtained in step 1630 toobtain a further or twice purified psychoactive alkaloid extract. Forthe repeated steps in these embodiments, the resin may be the same or adifferent resin, and the solvent may be the same or a different solvent.While the purified psychoactive alkaloid extract may have a lowpsychoactive alkaloid content, this may be increased by evaporation ofsome or all of the solvent.

F. Standardization

Standardization of Psychoactive Alkaloid 1

In one embodiment, referring to FIG. 14 , a process for obtaining thecomposition is shown. The process includes the step 1400 of extracting apsychoactive alkaloid from a psychoactive alkaloid source to obtain apsychoactive alkaloid extract. The extract from the psychoactivealkaloid source may be a fluid, as either a liquid or a slurry, or ismade into a fluid by the addition of a solvent. In one embodiment, theextraction step 1400 is followed by completely or partiallyconcentrating the obtained psychoactive alkaloid extract (or solution)by evaporation of the solvent from the extract. In other embodiments,partially or completely evaporating the solvent may be considered to bepart of the extraction step 1400. If the solvent from the extract hasbeen completely evaporated, then water, more solvent, or another solventis added back.

In step 1410, the extract obtained is filtered, followed byconcentration to obtain a concentrated psychoactive alkaloid extract.Filtration is performed by any suitable known technique.

In step 1420, the concentrated psychoactive alkaloid extract is thenstandardized by adding one or more excipients to the extract, followedby drying to obtain the standardized psychoactive alkaloid composition.The concentration of alkaloids in the extract is measured, and theproportion of dry weight in the extract is calculated. Based on thisconcentration and dry weight content, the amount of excipient to beadded is chosen to result in a powered composition with a specificamount of psychoactive alkaloid when the concentrated extract is dried.

The drying can be achieved by any technique known in the art for dryingmoist compositions including, for example, spray drying or freezedrying.

Standardization of Psychoactive Alkaloid 2

Referring to FIG. 11 , the present invention also relates to a processof obtaining a standardized, purified, psychoactive alkaloid extract. Inone embodiment, the process includes, in step 1100, concentrating thepurified psychoactive alkaloid solution to obtain a purifiedpsychoactive alkaloid slurry. The slurry is then standardized, in step1110, to obtain a standardized psychoactive alkaloid extract.

In one embodiment, the standardizing step 1110 includes addingexcipients to the purified psychoactive alkaloid slurry to obtain thestandardized psychoactive alkaloid extract. The concentration ofalkaloids in the slurry is measured, and the proportion of dry weight inthe slurry is calculated. Knowing this concentration and the dry weightcontent, the amounts of excipients are chosen to result in a powder ofknown alkaloid concentration after the solvent in the slurry has beenevaporated.

In one embodiment, the excipients are selected from silicon dioxide,ascorbic acid, maltodextrin from corn, potato or tapioca for example,gum arabic, microcrystalline cellulose, sodium benzoate, sodiumphosphate, sodium citrate, rice hulls, and rice. A combination of any ofthese excipients may be used.

Depending on the concentration of the purified psychoactive alkaloidslurry and the quantity of excipients added, the standardizedpsychoactive alkaloid extract may have a psychoactive alkaloidconcentration ranging from 0.1-99% by weight, and the concentration maybe specified to two decimal places or two significant figures. For thehighest percentage, only 1% of the standardized psychoactive extractwill be excipient.

In exemplary embodiments, the standardized psychoactive alkaloidextracts have psychoactive alkaloid concentrations of 5.00% by weight,54% by weight, and 68% by weight.

Numbered Embodiments

1. A psychoactive alkaloid composition comprising of, by weight:0.1-99.9% of a psychoactive alkaloid extract; and one or morepreservatives up to 10%, a flow agent up to 2%, 0-94% of one or morecarriers, or any combination thereof.

2. The composition of embodiment 1, comprising 2-99.7% of thepsychoactive alkaloid extract.

3. The composition of embodiment 1, comprising an antioxidant up to 0.5%by weight.

4. The composition of embodiment 1, comprising a bioavailability agentup to 0.5% by weight.

5. The composition of embodiment 1, wherein the psychoactive alkaloidextract has a psychoactive alkaloid concentration ranging from 0.1% to99% by weight of the extract.

6. The composition of embodiment 5 wherein the one or more preservativesare selected from ascorbic acid, citric acid, lactose, vitamin A,vitamin E, retinyl palmitate, selenium, sodium citrate, sodiumascorbate, calcium ascorbate, sodium benzoate, and potassium benzoate.

7. The composition of embodiment 1, wherein the psychoactive alkaloidextract has a psychoactive alkaloid concentration ranging from 0.1% to20% by weight of the extract.

8. The composition of embodiment 1, wherein the psychoactive alkaloidextract is a purified psychoactive alkaloid extract, and the purifiedpsychoactive alkaloid extract has a psychoactive alkaloid concentrationranging from 10% to 99% by weight.

9. The composition as in embodiment 1, in a powder form.

10. The composition of embodiment 1, comprising 10% or more of thecarrier.

11. The composition of embodiment 1, wherein the psychoactive alkaloidis psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin,aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT(5-methoxy-N.Ndimethyltryptamine), N,N-dimethyltryptamine (DMT),4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine ergine (LSA),ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acidhydroxyethylamide (LSH), elymoclavine, ergometrinine, and/orchanoclavine, or any combination selected therefrom.

12. The composition of embodiment 1, wherein the psychoactive alkaloidextract comprises naturally occurring substances selected from the groupconsisting of fats, sugars, carbohydrates, chitin, chitosan, minerals,waxes and proteins.

13. The composition of embodiment 10, wherein the naturally occurringsubstances are present in the psychoactive alkaloid extract in aconcentration ranging from 1%-99.9% by weight.

14. The composition of embodiment 1, wherein the psychoactive alkaloidextract is from fungi.

15. The composition of embodiment 14, wherein the psychoactive alkaloidextract is from Psilocybe cyanescens, Psilocybe cubensis, Amanitamuscaria, or any selection therefrom.

16. The composition of embodiment 1, wherein the psychoactive alkaloidextract is from psychoactive plants.

17. The composition of embodiment 16, wherein the psychoactive alkaloidextract is from Anadenanthera colubrina.

18. The composition of embodiment 16, wherein the psychoactive alkaloidextract is from Anadenanthera peregrina.

19. The composition of embodiment 1, wherein the psychoactive alkaloidextract is from psychoactive animals.

20. The composition of embodiment 19, wherein the psychoactive alkaloidextract is from Incilius alvarius.

21. The composition of embodiment 1, wherein the psychoactive alkaloidextract is from psychoactive yeasts.

22. The composition of embodiment 1, wherein the flow agent is selectedfrom silicon dioxide, stearic acid, magnesium stearate, or talc.

23. The composition of embodiment 1, wherein the one or more carriersare selected from starch, maltodextrin, alpha and beta cyclodextrin,microcrystalline cellulose (MCC), gum arabic, xanthum gum, guar gum,mannitol, or cellulose gum.

24. The composition of embodiment 23, wherein the maltodextrin istapioca maltodextrin or rice maltodextrin.

25. The composition of embodiment 23, wherein the starch is potatostarch.

26. The composition of embodiment 1, wherein the flow agent is presentin the composition at 0.1 to 1.2%.

27. The composition of embodiment 1, wherein a first preservative of theone or more preservatives is present in the composition at 0.1 to 3%.

28. The composition of embodiment 27, wherein a second preservative ofthe one or more preservatives is present in the composition at 0.1 to3%.

29. The composition of embodiment 1, wherein a first carrier of the oneor more carriers is present in the composition at 10 to 20%.

30. The composition of embodiment 29, wherein a second carrier of theone or more carriers is present in the composition at 10 to 20%.

31. The composition of embodiment 1, comprising: the flow agent presentin the composition at 0.1 to 1.2%; the one or more preservatives presentin the composition at 0.1 to 2%; and the one or more carriers present inthe composition at 10 to 20%.

32. The composition of embodiment 1, wherein: the flow agent is silicondioxide; the carrier comprises maltodextrin and mannitol; and the one ormore preservatives comprise ascorbic acid and citric acid.

33. The composition of embodiment 32, wherein the silicon dioxide ispresent in the composition at 0.1 to 1.2%.

34. The composition of embodiment 32, wherein the ascorbic acid ispresent in the composition at 0.1 to 2%.

35. The composition of embodiment 32, wherein the citric acid is presentin the composition at 0.1 to 2%.

36. The composition of embodiment 32, wherein the maltodextrin ispresent in the composition at 10 to 20%.

37. The composition of embodiment 32, wherein the mannitol is present inthe composition at 10 to 20%.

38. The composition of embodiment 1, wherein: the flow agent is silicondioxide; the carrier comprises starch and mannitol; and the one or morepreservatives comprise ascorbic acid and citric acid.

39. The composition of embodiment 38, wherein the silicon dioxide ispresent in the composition at 0.1 to 1.2%.

40. The composition of embodiment 38, wherein the ascorbic acid ispresent in the composition at 0.1 to 2%.

41. The composition of embodiment 38, wherein the citric acid is presentin the composition at 0.1 to 2%.

42. The composition of embodiment 38, wherein the starch is present inthe composition at 10 to 20%.

43. The composition of embodiment 38, wherein the mannitol is present inthe composition at 10 to 20%.

44. A method for generating a psychoactive alkaloid extract from apsychoactive organism, the method comprising: a. providing a biomass ofthe psychoactive organism; b. contacting the biomass with 10 to 100milliliters (mL) of solvent per gram (g) of the biomass; and c.evaporating the solvent from the biomass to yield the psychoactivealkaloid extract.

45. The method of embodiment 44, wherein the solvent is selected from100% methanol, an alcohol:water mixture wherein the alcohol comprises60% to 99% of the alcohol:water mixture, an alcohol:acid mixture whereinthe alcohol comprises 60% to 99% of the alcohol:acid mixture, andacidified water.

46. A method for generating a psychoactive alkaloid extract from apsychoactive organism, the method comprising: a. providing a biomass ofthe psychoactive organism; b. contacting the biomass with a solvent,wherein the solvent is selected from 100% methanol, an alcohol:watermixture wherein the alcohol comprises 60% to 99% of the alcohol:watermixture, an alcohol:acid mixture wherein the alcohol comprises 60% to99% of the alcohol:acid mixture, and acidified water; and c. evaporatingthe solvent from the biomass to yield the psychoactive alkaloid extract.

47. The method of embodiment 46, wherein the solvent is present at 10 to100 milliliters (mL) of solvent per gram (g) of the biomass.

48. The method of any one of embodiments 44 to 47, wherein the solventis present at 10 to 60 mL of solvent per gram of the biomass.

49. The method of any one of embodiments 44 to 48, wherein the solventis present at 40 to 60 mL of solvent per gram of the biomass.

50. The method of any one of embodiments 44 to 49, wherein the biomassof the psychoactive organism is dried prior to contacting with thesolvent.

51. The method of any one of embodiments 44 to 50, wherein the biomassof the psychoactive organism is reduced to a particle size of 6millimeters (mm) to 0.03 mm prior to contacting with the solvent.

52. The method of any one of embodiments 44 to 51, wherein the biomassof the psychoactive organism is reduced to a particle size of 1 mm to0.03 mm prior to contacting with the solvent.

53. The method of any one of embodiments 44 to 52, wherein the biomassof the psychoactive organism is reduced to a particle size of at least0.074 mm prior to contacting with the solvent.

54. The method of any one of embodiments 44 to 53, wherein the biomassof the psychoactive organism is contacted with the solvent at 5° C. to95° C.

55. The method of any one of embodiments 44 to 54, wherein the biomassof the psychoactive organism is contacted with the solvent at 20° C. to70° C.

56. The method of any one of embodiments 44 to 55, wherein the biomassof the psychoactive organism is contacted with the solvent at 25° C.

57. The method of any one of embodiments 44 to 56, wherein the biomassof the psychoactive organism is contacted with the solvent for 1 to 720minutes.

58. The method of any one of embodiments 44 to 57, wherein the biomassof the psychoactive organism is contacted with the solvent for 20 to 60minutes.

59. The method of any one of embodiments 44 to 58, wherein the biomassof the psychoactive organism is contacted with the solvent for 30minutes.

60. The method of any one of embodiments 44 to 59, wherein, following(b), the biomass is filtered through a filter.

61. The method of embodiment 60, wherein the filter comprises 1 micron(μm) to 10 μm mesh.

62. The method of any one of embodiments 44 to 61, wherein, following(b), the biomass is contracted with a second solvent.

63. The method of embodiment 62, wherein the second solvent is selectedfrom 100% methanol, an alcohol:water mixture wherein the alcoholcomprises 60% to 99% of the alcohol:water mixture, an alcohol:acidmixture wherein the alcohol comprises 60% to 99% of the alcohol:acidmixture, and acidified water.

64. The method of embodiment 62 or 63, wherein the second solvent ispresent at 10 to 100 milliliters (mL) of solvent per gram (g) of thebiomass.

65. The method of any one of embodiments 62 to 64, wherein the solventis present at 10 to 60 mL of solvent per gram of the biomass.

66. The method of any one of embodiments 62 to 65, wherein the solventis present at 40 to 60 mL of solvent per gram of the biomass.

67. The method of any one of embodiments 44 to 66, wherein the alcoholof the alcohol:water mixture, the alcohol:acid mixture, or both, is aC1-C4 primary aliphatic alcohol.

68. The method of embodiment 67, wherein the C1-C4 primary aliphaticalcohol is ethanol or methanol.

69. The method of any one of embodiments 44 to 68, wherein the acid inthe alcohol:acid mixture, the acidified water, or both, is acetic acid,adipic acid, ascorbic acid, phosphoric acid, ammonium aluminum sulphate,ammonium citrate dibasic, ammonium citrate monobasic, calcium citrate,calcium fumarate, calcium gluconate, calcium phosphate dibasic, calciumphosphate, hydrochloric acid, sulphuric acid monobasic, calciumphosphate tribasic, citric acid, fumaric acid, gluconic acid, magnesiumfumarate, malic acid, phosphoric acid, potassium acid tartrate,potassium citrate, potassium fumarate, sodium citrate, sodium fumarate,sodium gluconate, sodium lactate, sodium potassium hexametaphosphate,sodium potassium tartrate, sodium potassium tripolyphosphate, sodiumpyrophosphate tetrabasic, sodium tripolyphosphate, tartaric acid, andany combination therefrom.

70. The method of any one of embodiments 44 to 68, wherein the solvent,second solvent, or both is buffered to a pH of either 4 or less, or 10or greater.

71. The method of embodiment 70, wherein the solvent, second solvent, orboth is buffered with ammonium bicarbonate, ammonium carbonate, ammoniumhydroxide, calcium acetate, calcium carbonate, calcium chloride, calciumhydroxide, calcium lactate, calcium oxide, calcium phosphate, dibasic,calcium phosphate monobasic, magnesium carbonate, potassium aluminumsulphate, potassium bicarbonate, potassium carbonate, potassiumhydroxide, potassium lactate, potassium phosphate, dibasic, potassiumpyrophosphate, tetrabasic, potassium phosphate tribasic, potassiumtripolyphosphate, sodium acetate, sodium acid pyrophosphate, sodiumaluminum phosphate, sodium aluminum sulphate, sodium bicarbonate, sodiumbisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, and any combination therefrom.

72. The method of embodiment 70 or 71, wherein the solvent, secondsolvent, or both is buffered with acetic acid, adipic acid, ascorbicacid, phosphoric acid, ammonium aluminum sulphate, ammonium citratedibasic, ammonium citrate monobasic, calcium citrate, calcium fumarate,calcium gluconate, calcium phosphate dibasic, calcium phosphate,hydrochloric acid, sulphuric acid monobasic, calcium phosphate tribasic,citric acid, fumaric acid, gluconic acid, magnesium fumarate, malicacid, phosphoric acid, potassium acid tartrate, potassium citrate,potassium fumarate, sodium citrate, sodium fumarate, sodium gluconate,sodium lactate, sodium potassium hexametaphosphate, sodium potassiumtartrate, sodium potassium tripolyphosphate, sodium pyrophosphatetetrabasic, sodium tripolyphosphate, tartaric acid, and any combinationtherefrom.

73. The method of any one or embodiments 44 to 72, wherein thepsychoactive alkaloid is psilocybin, psilocin, baeocystin,norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine,5-MeO-DMT (5-methoxy-N.Ndimethyltryptamine), N,N-dimethyltryptamine(DMT), 4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine ergine(LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acidhydroxyethylamide (LSH), elymoclavine, ergometrinine, and/orchanoclavine, or any combination selected therefrom.

74. The method of any one or embodiments 44 to 72, wherein the solventhas a pH of 10 or greater and the psychoactive alkaloid extractcomprises greater than 50% of the phosphorylated psychoactive alkaloid.

75. The method of embodiment 74, wherein the psychoactive alkaloidextract comprises greater than 90% of a phosphorylated psychoactivealkaloid.

76. The method of embodiment 74 or 75, wherein the phosphorylatedalkaloid is psilocybin, baeocystin, norbaeocystin, aeruginascin, or anycombination therefrom.

77. The method of any one or embodiments 44 to 72, wherein the solventhas a pH of 4 or less and the psychoactive alkaloid extract comprisesgreater than 50% of a dephosphorylated psychoactive alkaloid.

78. The method of embodiment 77, wherein the psychoactive alkaloidextract comprises greater than 90% of the dephosphorylated psychoactivealkaloid.

79. The method of embodiment 77 or 78, wherein the dephosphorylatedalkaloid is psilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination therefrom.

80. The method of any one or embodiments 44 to 79, wherein thepsychoactive organism is a plant, animal, fungus, Protist, or bacterium.

81. The method of any one or embodiments 44 to 80, wherein thepsychoactive organism is Psilocybe cyanescens, Psilocybe cubensis,Amanita muscaria, or any selection therefrom.

82. The method of any one or embodiments 44 to 80, wherein thepsychoactive organism is Anadenanthera colubrina or Anadenantheraperegrina.

83. The method of any one or embodiments 44 to 80, wherein thepsychoactive organism is Incilius alvarius.

84. The method of any one or embodiments 44 to 80, wherein thepsychoactive organism is yeast.

85. A process for forming an extract of psychoactive alkaloids frompsychoactive organisms comprising the steps of: soaking a biomass ofdried, raw psychedelic fungus in a solvent selected from the groupconsisting of ethanol, a water-ethanol mixture, methanol, and awater-methanol mixture in order to dissolve the psychoactive alkaloidsin the solvent; filtering an undissolved portion of the biomass from thesolvent; evaporating the solvent sufficiently to remove the solventcompletely, leaving a concentrated slurry or a residue that is convertedto the concentrated slurry by adding water thereto: and standardizingthe concentrated slurry by adding thereto a quantity of carrier measuredto achieve a specified purity of extract.

86. The process of embodiment 85, wherein the standardizing comprises:measuring a psychoactive alkaloid content in the concentrated slurry;and using the psychoactive alkaloid content, the specified purity and avolume of the concentrated slurry to determine the quantity of carrier.

87. The process of embodiment 85, comprising drying the concentratedslurry to result in the extract, wherein the extract is a powderedextract.

88. The process of embodiment 85, wherein the solvent is a water-ethanolor water-methanol alkaline buffered solution.

89. The process of embodiment 88, wherein the solvent has a pH of 11-12.

90. The process of embodiment 88, wherein the solvent is buffered withsodium hydroxide, the process comprising, between the filtering andevaporating steps, adjusting the solvent to a pH of 4-9 using phosphoricacid.

91. The process of embodiment 85, wherein the solvent is a water-ethanolor water-methanol acid buffered solution.

92. The process of embodiment 91, wherein the solvent has a pH of 1.8-3.

93. The process of embodiment 91, wherein the solvent is buffered withcitric acid, the process comprising, between the filtering andevaporating steps, adjusting the solvent to a pH of 4-9 using sodiumhydroxide.

94. The process of embodiment 85, wherein the solvent comprises 100%reverse osmosis water.

95. The process of embodiment 85, wherein the soaking is at atemperature of 5-95° C.

96. The process of embodiment 85, comprising applying a pressure of 50kPa-100 MPa to the solvent during the soaking step.

97. The process of embodiment 85, comprising agitating the solventduring the soaking step, wherein the soaking step has a duration of 10minutes to 12 hours.

98. The process of embodiment 85, wherein the psychedelic organism is aplant, animal, fungus, Protist, or bacterium.

99. The process of embodiment 93, wherein the fungus comprises Amanitamuscaria, Psilocybe cubensis, Psilocybe cyanescens, or any combinationthereof.

100. The process of embodiment 85, wherein the psychoactive alkaloidscomprise psilocybin, psilocin, baeocystin, norbaeocystin, ibotenic acidor any mixture thereof.

101. The process of embodiment 85, wherein the solvent to biomass ratiois in a range from 1 L:1 kg to 50 L:1 kg.

102. The process of embodiment 85, wherein the specified purity is0.1-10%.

103. The process of embodiment 85, wherein the specified purity isspecified as a percentage with a precision of two decimal places.

104. The process of embodiment 85, wherein the carrier comprisesascorbic acid, silicon dioxide, maltodextrin, gum arabic,microcrystalline cellulose, sodium citrate, sodium benzoate, sodiumphosphate, rice, rice hulls, or any combination of the foregoing.

105. The process of embodiment 85, comprising: repeating, using furthersolvent, the soaking and filtering steps for the filtered biomass; andcombining the filtered solvent with the filtered further solvent.

106. A process for obtaining a purified psychoactive alkaloid solution,the process comprising: extracting a psychoactive alkaloid from apsychoactive alkaloid source to obtain a psychoactive alkaloid extract;contacting the psychoactive alkaloid extract with an adsorbent materialto obtain an adsorbed psychoactive alkaloid; and eluting the adsorbedpsychoactive alkaloid using a solvent to obtain a purified psychoactivealkaloid solution, wherein the solvent is water, an organic solvent or acombination thereof, under basic, acidic or neutral pH.

107. The process of embodiment 106, comprising, prior to the treatingstep, adding an acid or a base to the psychoactive alkaloid extract.

108. The process of embodiment 107, wherein, after adding the acid orbase, the psychoactive alkaloid extract has a pH ranging from 2.5-4.5 orfrom 9-10 respectively.

109. The process of embodiment 107, wherein the acid is selected fromthe group consisting of acetic acid, adipic acid, ascorbic acid,phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic,ammonium citrate monobasic, calcium citrate, calcium fumarate, calciumgluconate, calcium phosphate dibasic, calcium phosphate, hydrochloricacid, sulphuric acid monobasic, calcium phosphate tribasic, citric acid,fumaric acid, gluconic acid, magnesium fumarate, malic acid, phosphoricacid, potassium acid tartrate, potassium citrate, potassium fumarate,sodium citrate, sodium fumarate, sodium gluconate, sodium lactate,sodium potassium hexametaphosphate, sodium potassium tartrate, sodiumpotassium tripolyphosphate, sodium pyrophosphate tetrabasic, sodiumtripolyphosphate, tartaric acid, and any combination therefrom.

110. The process of embodiment 107, wherein the base is selected fromthe group consisting of ammonium bicarbonate, ammonium carbonate,ammonium hydroxide, calcium acetate, calcium carbonate, calciumchloride, calcium hydroxide, calcium lactate, calcium oxide, calciumphosphate, dibasic, calcium phosphate monobasic, magnesium carbonate,potassium aluminum sulphate, potassium bicarbonate, potassium carbonate,potassium hydroxide, potassium lactate, potassium phosphate, dibasic,potassium pyrophosphate, tetrabasic, potassium phosphate tribasic,potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate,sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate,sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodiumhydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphatemonobasic, sodium phosphate tribasic, and any combination therefrom.

111. The process of embodiment 106, wherein the adsorbent material is agel resin, a macroporous resin, or a combination thereof.

112. The process of embodiment 111, wherein the macroporous resin is anon-ionic macroporous resin, an ion-exchange macroporous resin, or acombination thereof.

113. The process of embodiment 106, wherein the psychoactive alkaloidsource comprises psilocybin, psilocin, baeocystin, norbaeocystin,norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT(5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine(LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acidhydroxyethylamide (LSH), elymoclavine, ergometrinine, chanoclavine, orany combination therefrom.

114. The process of embodiment 106, wherein the organic solvent isselected from a group consisting of C1-4 primary aliphatic alcohols,C3-4 ketones, and any combination therefrom.

115. The process of embodiment 106, wherein the process comprisesfurther purifying the obtained purified psychoactive alkaloid solutionby repeating, with the obtained purified psychoactive alkaloid solution,the treating step with a different adsorbent material and the elutingstep with another solvent.

116. The process of embodiment 106, comprising: evaporating a portion ofsolvent from the purified psychoactive alkaloid solution to obtain apurified psychoactive alkaloid slurry.

117. The process of embodiment 116, wherein the purified psychoactivealkaloid slurry comprises 5% by weight or more of a psychoactivealkaloid.

118. The process of embodiment 116, comprising:

standardizing the purified psychoactive alkaloid slurry by addingthereto a quantity of excipient measured to provide a specificconcentration of psychoactive alkaloid when the purified psychoactivealkaloid slurry is dried; and drying the purified psychoactive alkaloidslurry by evaporating the remaining portion of the solvent to obtain astandardized, purified, powdered psychoactive alkaloid extract havingthe specific concentration of psychoactive alkaloid.

119. The process of embodiment 116, wherein: the psychoactive alkaloidcomprises psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin,aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT(5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine(LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acidhydroxyethylamide (LSH), elymoclavine, ergometrinine, chanoclavine, orany combination therefrom; and the standardized, purified, powderedpsychoactive alkaloid extract has a psychoactive alkaloid concentrationranging from 0.1-99% by weight.

120. The process of embodiment 118, wherein the excipient is selectedfrom the group consisting of silicon dioxide, ascorbic acid,maltodextrin, gum arabic, microcrystalline cellulose, sodium benzoate,sodium phosphate, sodium citrate, rice hulls, rice and any combinationtherefrom.

121. The process of embodiment 106, comprising: prior to the treatingstep: adding an acid to the psychoactive alkaloid extract to bring itspH to 4±0.5; and removing solids from the psychoactive alkaloid extract;and after the treating step and before the eluting step: washing theadsorbent material with purified water; wherein: the adsorbent materialis a non-ionic macroporous resin; and the solvent used for the elutingstep is a hydro-ethanol solvent.

122. The process of embodiment 121, wherein the hydro-ethanol solvent is5% ethanol.

123. The process of embodiment 106, comprising: prior to the treatingstep: adding an acid to the psychoactive alkaloid extract to bring itspH to 3±0.5; after the treating step and before the eluting step:washing the adsorbent material with 100% ethanol, wherein the adsorbentmaterial is a macroporous strong cation exchange resin in an H+ or anNa+ form; and washing the adsorbent material with purified water;wherein the solvent used for the eluting step is 2% hydrochloric acidand 80% ethanol; and after the eluting step: adding alkali to thepurified psychoactive alkaloid solution to bring its pH to 4±0.5;removing solids from the purified psychoactive alkaloid solution;evaporating a portion of the solvent from the purified psychoactivealkaloid solution; removing further solids from the purifiedpsychoactive alkaloid solution; treating the purified psychoactivealkaloid extract with a non-ionic macroporous resin to obtain a secondadsorbed psychoactive alkaloid; washing the non-ionic macroporous resinwith purified water; and eluting the second adsorbed psychoactivealkaloid from the non-ionic macroporous resin using a hydro-ethanolsolvent to obtain a twice purified psychoactive alkaloid solution.

124. The process of embodiment 106, comprising: prior to the treatingstep: adding a base to the psychoactive alkaloid extract to bring its pHto 9.5±0.5; after the treating step and before the eluting step: washingthe adsorbent material with 100% ethanol, wherein the adsorbent materialis a macroporous strong anion exchange resin in an OH− or a Cl− form;and washing the adsorbent material with purified water; wherein thesolvent used for the eluting step is 2% sodium chloride and 80% ethanol;and after the eluting step: adding acid to the purified psychoactivealkaloid solution to bring its pH to 4±0.5; removing solids from thepurified psychoactive alkaloid solution; evaporating a portion of thesolvent from the purified psychoactive alkaloid solution; removingfurther solids from the purified psychoactive alkaloid solution;treating the purified psychoactive alkaloid extract with a non-ionicmacroporous resin to obtain a second adsorbed psychoactive alkaloid;washing the non-ionic macroporous resin with purified water; and elutingthe second adsorbed psychoactive alkaloid from the non-ionic macroporousresin using a hydro-ethanol solvent to obtain a twice purifiedpsychoactive alkaloid solution.

125. The process of embodiment 106, wherein the psychoactive alkaloidsource comprises psychoactive fungus and the extracting step comprises:drying and pulverizing the psychoactive alkaloid source to obtain adried biomass; heating the dried biomass in a first solvent to obtain afirst slurry, and filtering the first slurry to obtain a first filtrateand a first residue; heating the first residue in a second solvent toobtain a second slurry, and filtering the second slurry to obtain asecond filtrate and a second residue; and mixing the first filtrate andthe second filtrate to obtain the psychoactive alkaloid extract.

126. The process of embodiment 125, wherein: the first solvent and thesecond solvent are selected from a group consisting of a primaryaliphatic alcohol, a ketone, purified water, and any combinationtherefrom; and the heating is carried out at a temperature ranging from5-95° C. and for a time duration ranging from 10 minutes to 12 hours.

127. The process of embodiment 106, wherein the psychoactive alkaloidsource is Anadenanthera peregrina, the process comprising: prior to thetreating step: adding an acid to the psychoactive alkaloid extract tobring its pH to 4±0.5; and removing solids from the psychoactivealkaloid extract; and after the treating step and before the elutingstep: washing the adsorbent material with purified water then with 10%ethanol; wherein: the adsorbent material is a macroporous resin; and thesolvent used for the eluting step is 50% ethanol.

128. The process of embodiment 106, wherein the psychoactive alkaloidsource comprises a plant, animal, fungus, protist, or bacterium.

129. T The process of embodiment 106, wherein the psychoactive alkaloidsource comprises Psilocybe cyanescens, Psilocybe cubensis, Amanitamuscaria, or any selection therefrom.

130. The process of embodiment 106, wherein the psychoactive alkaloidsource comprises Anadenanthera colubrina or Anadenanthera peregrina.

131. The process of embodiment 106, wherein the psychoactive alkaloidsource comprises Incilius alvarius.

132. The process of embodiment 106, wherein the psychoactive alkaloidsource comprises yeast.

133. The process of embodiment 106, wherein the psychoactive alkaloidextract is contacted with the adsorbent material at a flow rate of 1 bedvolume per hour (BV/h) to 10 BV/h.

134. The process of embodiment 133, wherein the psychoactive alkaloidextract is contacted with the adsorbent material at a flow rate of 2 bedvolume per hour (BV/h) to 6 BV/h.

135. A process for obtaining a psychoactive alkaloid extract with adesired amount of a phosphorylated psychoactive alkaloid and a desiredamount of a dephosphorylated psychoactive alkaloid, the processcomprising: drying and pulverizing a psychoactive alkaloid source toobtain a dried powdered biomass; extracting a psychoactive alkaloid fromthe dried powdered biomass with an acidified solvent or a basifiedsolvent to obtain a psychoactive alkaloid liquid with a specific pH,wherein the specific pH is lower than 3.5 or greater than 10.5;adjusting the pH of the psychoactive alkaloid liquid to a pH rangingfrom 3.5-4.5; and evaporating the solvent from the psychoactive alkaloidliquid to obtain the psychoactive alkaloid extract with the desiredamount of the phosphorylated psychoactive alkaloid and the desiredamount of the dephosphorylated psychoactive alkaloid; wherein: thedesired amount of the phosphorylated psychoactive alkaloid is 0-100% byweight of a total phosphorylatable psychoactive alkaloid content in thepsychoactive alkaloid extract; and the desired amount of thedephosphorylated psychoactive alkaloid is the remainder of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract.

136. The process of embodiment 135, wherein the phosphorylated alkaloidis psilocybin, baeocystin, norbaeocystin, aeruginascin, or anycombination therefrom; and the dephosphorylated alkaloid is psilocin,norpsilocin, 4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine,or any combination therefrom.

137. The process of embodiment 135, wherein the psychoactive alkaloidsource comprises psilocybin, baeocystin, norbaeocystin, aeruginascin,psilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination therefrom.

138. The process of embodiment 135, wherein the extracting stepcomprises: mixing the dried powdered biomass with the acidified solventor the basified solvent to obtain a slurry; and filtrating the slurry toobtain a filtrate residue and the psychoactive alkaloid liquid.

139. The process of embodiment 138, wherein the extracting stepcomprises further extracting the psychoactive alkaloid by repeating,with the obtained filtrate residue, the extracting step with the same ora different acidified solvent, or the same or a different basifiedsolvent.

140. The process of embodiment 138, wherein after the mixing step theacidified solvent or the basified solvent, the slurry has a pH rangingfrom 0.5-3.5 or from 10.5-13.5 respectively.

141. The process of embodiment 135, wherein the acidified solvent is amixture of an acid; and a C1-C4 primary aliphatic alcohol, a C3-C4ketone, water, or any combination selected therefrom.

142. The process of embodiment 135, wherein the basified solvent is amixture of a base; and a C1-C4 primary aliphatic alcohol, a C3-C4ketone, water, or any combination selected therefrom.

143. The process of embodiment 135, wherein the extraction is performed:at a temperature ranging from 5-95° C.; and for a time period rangingfrom 10-720 minutes.

144. The process of embodiment 135, wherein the extraction is performedat a pressure ranging from 7 to 20,000 psi (50 kPa-138 MPa).

145. The process of embodiment 135, wherein the extraction is performedwith a solvent to solid proportion of 1 L:1 kg to 50 L:1 kg, wherein thesolid is the dried powdered biomass.

146. The process of embodiment 135, wherein the specific pH is lowerthan 3.5; and wherein: the desired amount of the phosphorylatedpsychoactive alkaloid is 0% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract, andthe desired amount of the dephosphorylated psychoactive alkaloid is 100%by weight of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract.

147. The process of embodiment 135, wherein the specific pH is greaterthan 10.5; and wherein the desired amount of the phosphorylatedpsychoactive alkaloid is 100% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract, andthe desired amount of the dephosphorylated psychoactive alkaloid is 0%by weight of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract.

148. The process of embodiment 135, wherein the specific pH is greaterthan 10.5, and a maximum desired amount of the phosphorylated alkaloidis limited by an amount of the dephosphorylated alkaloid in thepsychoactive alkaloid source.

149. The process of embodiment 135, wherein the specific pH is greaterthan 10.5, and wherein: the desired amount of the phosphorylatedpsychoactive alkaloid is 1-99% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract.

150. The process of embodiment 135, comprising: pausing the evaporatingstep when a portion of the solvent has been evaporated from thepsychoactive alkaloid liquid to obtain a psychoactive alkaloid slurry;standardizing the psychoactive alkaloid slurry by adding thereto ameasured quantity of one or more excipients to obtain a standardizedslurry with a specific amount of psychoactive alkaloid content; andcontinuing the evaporating step by drying the standardized slurry toobtain a psychoactive alkaloid composition comprising the psychoactivealkaloid extract, and one or more excipients; wherein a totalpsychoactive alkaloid content in the psychoactive alkaloid compositionis specified as a result of the standardizing step.

151. The process of embodiment 150, wherein the desired amount of thephosphorylated psychoactive alkaloid is 100% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid composition, the process comprising: preparing anotherpsychoactive alkaloid composition comprising another psychoactivealkaloid extract according to embodiment 150, wherein the desired amountof the dephosphorylated psychoactive alkaloid is 100% by weight of thetotal phosphorylatable psychoactive alkaloid content in the otherpsychoactive alkaloid extract; mixing the psychoactive alkaloidcomposition and the other psychoactive composition in a measured ratioto obtain a psychoactive alkaloid composition comprising thephosphorylated psychoactive alkaloid of the psychoactive alkaloidcomposition and the dephosphorylated psychoactive alkaloid of the otherpsychoactive alkaloid composition in a specific ratio; wherein thespecific ratio of phosphorylated psychoactive alkaloid todephosphorylated psychoactive alkaloid ranges from 1:1000 to 1000:1.

152. A process for obtaining a psychoactive alkaloid composition with aspecific ratio of a phosphorylated psychoactive alkaloid to adephosphorylated psychoactive alkaloid, the process comprising:extracting a psychoactive alkaloid from a dried powdered biomass with abasified solvent to obtain a psychoactive alkaloid liquid with a pHgreater than 10.5, wherein a majority of a total phosphorylatablepsychoactive alkaloid content is the phosphorylated alkaloid and aremainder thereof is the dephosphorylated alkaloid; adjusting the pH ofthe psychoactive alkaloid liquid to a pH ranging from 3.5-4.5;extracting another psychoactive alkaloid from another dried powderedbiomass with an acidified solvent to obtain another psychoactivealkaloid liquid with a pH lower than 3.5, wherein all of a totalphosphorylatable psychoactive alkaloid is the dephosphorylated alkaloid;adjusting the pH of the other psychoactive alkaloid liquid to a pHranging from 3.5-4.5; evaporating a portion of the basified solvent fromthe psychoactive alkaloid liquid and a portion of the acidified solventfrom the other psychoactive alkaloid liquid to obtain a psychoactivealkaloid extract slurry and another psychoactive alkaloid extract slurryrespectively; mixing measured portions of the psychoactive alkaloidextract slurry and the other psychoactive alkaloid extract slurry toobtain a bulk psychoactive alkaloid extract slurry comprising thephosphorylated psychoactive alkaloid and the dephosphorylatedpsychoactive alkaloid in the specific ratio; standardizing the bulkpsychoactive alkaloid extract slurry by adding thereto a measuredquantity of one or more excipients to obtain a standardized bulk slurry;and drying the standardized bulk psychoactive alkaloid slurry to obtainthe psychoactive alkaloid composition, wherein the phosphorylatedpsychoactive alkaloid and the dephosphorylated psychoactive alkaloid arein the specific ratio; wherein the specific ratio of phosphorylatedpsychoactive alkaloid to dephosphorylated psychoactive alkaloid rangesfrom 1:1000 to 1000:1.

153. A psychoactive alkaloid composition comprising: a psychoactivealkaloid extract comprising a desired amount of a phosphorylatedpsychoactive alkaloid and a desired amount of a dephosphorylatedpsychoactive alkaloid, wherein: the desired amount of the phosphorylatedpsychoactive alkaloid is 0-100% by weight of a total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract, andthe desired amount of the dephosphorylated psychoactive alkaloid is theremainder of the total phosphorylatable psychoactive alkaloid content inthe psychoactive alkaloid extract; and one or more excipients.

154. The composition of embodiment 153, wherein the composition is inpowder form.

155. The composition of embodiment 153, wherein: the desired amount ofthe phosphorylated psychoactive alkaloid is 0% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is 100% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract.

156. The composition of embodiment 153, wherein: the desired amount ofthe phosphorylated psychoactive alkaloid is 100% by weight of the totalphosphorylatable psychoactive alkaloid content in the psychoactivealkaloid extract, and the desired amount of the dephosphorylatedpsychoactive alkaloid is 0% by weight of the total phosphorylatablepsychoactive alkaloid content in the psychoactive alkaloid extract.

157. The composition of embodiment 153, wherein: the phosphorylatedalkaloid is psilocybin, baeocystin, norbaeocystin, aeruginascin, or anycombination selected therefrom; and the dephosphorylated alkaloid ispsilocin, norpsilocin, 4-hydroxytryptamine,N,N,N-trimethyl-4-hydroxytryptamine, or any combination selectedtherefrom.

158. A psychoactive alkaloid composition with a specific ratio of aphosphorylated psychoactive alkaloid and a dephosphorylated psychoactivealkaloid, the composition comprising: a psychoactive alkaloid extracthaving a total phosphorylatable psychoactive alkaloid content of 100% ofa phosphorylated psychoactive alkaloid; another psychoactive alkaloidextract having a total phosphorylatable psychoactive alkaloid content of100% of a dephosphorylated psychoactive alkaloid; and one or moreexcipients; wherein the psychoactive alkaloid extract and the otherpsychoactive alkaloid extract are present in a proportion such that thespecific ratio of phosphorylated psychoactive alkaloid to phosphorylatedpsychoactive alkaloid ranges from 1:1000 to 1000:1.

Examples

In order to further illustrate the present invention, the followingspecific examples are given with the understanding that these examplesare intended only to be illustrations without serving as a limitation onthe scope of the present invention. All parameters, dimensions,materials, quantities, and configurations described herein are examplesonly and may be changed depending on the specific embodiment.Accordingly, the scope of the invention is to be construed in accordancewith the substance defined by the claims. The process may be scaled upusing larger quantities and modified apparatus.

Although the examples of the present invention have been formulatedspecifically using Psilocybe cubensis as a source to obtain apsychoactive alkaloid extract, the extract including psilocybin andpsilocin, other sources are possible. A person skilled in the art wouldappreciate that the Psilocybe cubensis can be readily substituted byother sources of psychoactive alkaloids to obtain a variety of otherpsychoactive alkaloids having similar properties, such as psilocybin,psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin,bufotenin, bufotenidine, 4-hydroxytryptamine, 5-MeO-DMT(5-methoxy-N,N-dimethyltryptamine), N,N-dimethyltryptamine (DMT),N,N,N-trimethyl-4-hydroxytryptamine, ergine (LSA), ergonovine,ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide(LSH), elymoclavine, ergometrinine, chanoclavine, or any combinationtherefrom, to result in compositions with similar efficacy andefficiency as well. For example, mushrooms from the genus Conocybe,Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina,Pluteus, Psilocybe, or any combination therefrom may be used. Forexample, Psilocybe cyanescens and Amanita muscaria fungi may be used.For example, the venom of the toad Incilius alvarius, the Anadenantheracolubrina tree or the Anadenanthera peregrina tree may be used as othersources of psychoactive alkaloids. Note that the lists of sources andpsychoactive alkaloids are included to provide examples and arenon-exhaustive lists.

Example 1: Preparation of Psychoactive Alkaloid Extract

Referring to FIG. 12 , 2.5 kg of fresh Psilocybe cubensis (caps, stemsand gills) was taken (step 1200) and dried (step 1201) in a forced airoven at 25° C. for 5-10 hours. A mass of 140 g of dried biomass wasobtained. The dried biomass was pulverized (step 1202) to a size of 200mesh with a hammer mill to result in a dried, powdered biomass. Thedried, powdered biomass was placed in an agitated, heat-controlledextraction vessel with 5 kg of a hydro-ethanol mixture, with 3 partsethanol to 1 part water by weight, as a solvent (step 1203). Theextraction (step 1204) was carried out for 4 hours at a controlledtemperature of 70° C. to obtain an extract in the form of a slurry. Theextraction slurry was filtered (step 1205) while it was hot, andfiltrate A was collected. The filter residue was retained (step 1206)and placed back into the extraction vessel, followed by addition (step1207) of another 5 kg of 3:1 ethanol:water mixture by weight as asolvent. The extraction was repeated (step 1208). The temperature ofextraction was again carried out at 70° C. for a duration of 4 hours.The obtained extraction slurry was filtered (step 1209) while hot andfiltrate B was collected. Filtrate A and filtrate B from the first andsecond extractions were mixed (step 1210). Using a rotary evaporator,the mixture was then partially concentrated by evaporation (step 1211)of the solvent from the combined filtrates to provide a 2.5 liter volumeof psychoactive alkaloid extract solution. Step 1211 is similar to step1010 of FIG. 10 .

Example 2: Preparation of Psychoactive Alkaloid Extract

In another example, the process of Example 1 was followed, except thatthe combined filtrates A and B were left to cool to room temperature,and any precipitate that formed was filtered out and discarded.

Example 3. Preparation of Anadenanthera peregrina Seed Extract

1.00 kg of dried Anadenanthera peregrina seeds were pulverized to a sizeof 200 mesh with a grinder. The dried powdered biomass was placed intoan agitated, heat-controlled vessel with 20 kg of solvent. In thisembodiment, the solvent was a hydro-ethanol mixture of 4 parts ethanolto 1 part water by weight. The extraction was controlled to a constant70° C., and the time of extraction was 4 hours. The extraction slurrywas filtered while hot, and the filter residue was placed back into theextraction vessel and extracted again with an additional 10 kg of 4:1ethanol:water mixture by weight. The temperature of extraction was again70° C. and the time was 4 hours. The extraction slurry was filteredwhile hot and the filtrates from the first and second extractions weremixed together. The resulting bulk filtrate was immediately placed intoan evaporation still and the solvent was removed until the final volumeof the filtrate was reduced to about 6 liters, which resulted in asolids concentration in the filtrate of 6.8%.

Example 4: Extraction Using a Solvent Mixture of Ethanol (0-100 wt %)and Water

Referring to FIG. 3 , a process is shown for the extraction ofpsychoactive compounds from Psilocybe cubensis using a generalhydro-ethanol solvent. The solvent may range from a percentage of <1% ofethanol in water to 100% ethanol.

In step 300, 2.5 kg of raw psilocybin mushrooms from the Psilocybecubensis species was provided. In step 310, the raw Psilocybe cubensiswas dried in a forced air oven at 25° C. for 10 hours. In step 320, theresulting dried biomass was ground in a hammer mill or the equivalent,to particle size of 200 mesh.

In step 330, 5 kg of solvent, having a 0-100% ethanol concentration wasadded to an extraction vessel into which the ground biomass was placed.The extraction vessel was an agitated, heat-controlled vessel.

In step 340, the extraction proceeds as the biomass was soaked. Thetemperature of the extraction was elevated above room temperature to 70°C. Temperature and pressure, if applied, were generally selected so thatthe solvent does not boil if elevated temperatures were used. Theduration of the extraction was 4 hours.

In the step 350, the extraction slurry was filtered to remove residuewith undissolved Psilocybe cubensis from the filtrate. The residue maybe treated with another extraction step if desired, and if so, thefiltrate from the subsequent step was combined with the filtrate fromthe first filtration.

In step 360, the solvent from the filtrate was partially evaporatedusing a rotary evaporator. The resulting concentrated slurry wassubjected to a standardization process in step 370. The standardizedconcentrated slurry was then dried using a bench-top spray dryer in step380 to result in a powder with an accurately determined concentration byweight of psychoactive alkaloids.

Example 5: Extraction Using a Solvent Mixture of Ethanol and Water (3:1wt %)

Referring to FIG. 2 , an exemplary detailed process is shown for theextraction of psychoactive compounds from Psilocybe cubensis mushroomsusing a 75% ethanol solvent.

In step 200, 2.5 kg of raw psilocybin mushrooms from the Psilocybecubensis species was provided. In step 201, the raw psilocybin mushroomswere dried in a forced air oven at 25° C., for 10 hours. The aim was todry the mushrooms so as not to significantly reduce their psychoactivealkaloid concentration. For example, if too high a temperature or toolong a time at a specific temperature were used, the alkaloids may startto decompose. The resulting, dried biomass was 140 g. In step 202, thedried biomass was ground using a hammer mill or the equivalent, to aparticle size of 200 mesh.

In step 203, a 5 kg quantity of the 75% (by weight) ethanol solvent,formed by mixing 3 parts of ethanol to 1 part of water by weight, wasplaced in an extraction vessel. The dried, ground biomass was alsoplaced in the extraction vessel, which was heat-controlled and agitated.

The extraction proceeds in step 204 as the biomass soaks in the solvent.The temperature of the extraction process was 70° C., and the durationof extraction was 4 hours. The temperature remained constant during theextraction process.

In step 205, the resulting mixture of biomass solids and solvent withdissolved extract, was filtered while still hot, i.e. still at 70° C.,or slightly lower due to ambient cooling. This removed a residue withundissolved psilocybin mushroom components from the filtrate. The filterused was a 10 μm sieve. The filtrate from this step was filtrate A. Instep 206, the residue was retained and placed back into the extractionvessel. In step 207, another 5 kg of 75% ethanol was added to theretained residue.

In step 208, the extraction process of the residue continued at the sametemperature as for the initial extraction step, i.e. at 70° C., for atime of 4 hours. Again, the temperature remained constant during theextraction process.

In step 209, the second resulting mixture, of biomass solids and solventwith dissolved extract, was filtered to remove the residue of unwantedsolid material. The filter used was a 10 μm sieve. Note that in otherembodiments a differently sized filter may be used here or in the priorfiltration step, or the liquid may be decanted from the residue withoutfiltering. In some embodiments, a centrifuge may be used to helpseparate the liquid from the residue. Filtrate B from the secondfiltration process may have a lower concentration of psychoactivecompounds than filtrate A from the first filtration step. Filtrates Aand B were then mixed in step 210 to result in bulk filtrate C. Moreextract can be obtained by splitting the solvent into two or morebatches and using each one sequentially to soak the biomass, compared tousing a single volume of solvent.

The bulk filtrate C was then processed with a rotary evaporator in step211 to remove solvent until the volume of filtrate C is 2.5 liters. Atthis point, the reduced amount of filtrate C was a concentrated slurry,due to the precipitation of water-insoluble components, for example.

The volume of 2.5 L was chosen because the mixture now has a low enoughethanol content that the carriers can be mixed in. By preferentiallyremoving ethanol over water, which occurs naturally during theevaporation, it also gives the later spray-drying step a lower risk ofexplosion compared to if a 75% ethanol slurry were sprayed directly.

In step 212, after some of the solvent has been removed using the rotaryevaporator, the concentrated slurry was then standardized. Thestandardization process uses a titration procedure to determine theconcentration of the psychoactive alkaloids in the concentrated slurry.The standardization procedure entails adjusting the concentration ofpsychoactive alkaloids the concentrated slurry to a desired target, suchas 1.00% by dry weight. In this example, 4.7 g of ascorbic acid, 1.9 gof SiO₂ and 47 g of maltodextrin were added to the concentrated slurry.

In step 213, after the standardization process, the standardizedconcentrated slurry was dried using a bench-top spray dryer. Thisresulted in 100 g of powdered psilocybin mushroom extract with a totalalkaloid concentration of 1.00% by weight. As can be seen, the purity ofthe extract can be defined as a percentage to a precision of two decimalplaces.

Example 6: Extraction Using a Buffered Solvent Mixture of Ethanol andWater (3:1 wt %) (Alkaline Solvent)

Referring to FIG. 7 , a process is shown for the extraction ofpsychoactive compounds from Psilocybe cubensis mushrooms using abuffered alkaline solvent. In step 700, 2.5 kg of raw psilocybinmushrooms from the Psilocybe cubensis species was provided. In step 701,the raw Psilocybe cubensis was dried in a forced air oven at 25° C. for10 hours. The dried biomass was 140 g. In step 702, the dried biomasswas ground in a hammer mill or the equivalent, to a particle size of 200mesh.

In step 703, 5 liters of solvent was added with the biomass to anextraction vessel, which was heat-controlled and agitated. The solventwas a pH-adjusted, hydro-ethanol mixture. For its preparation, 200 g ofsodium hydroxide pellets were placed into a 5 L vessel, with 1.25 L ofreverse osmosis water followed by 3.75 L of ethanol. The contents weremixed until completely dissolved. The pH of this solution was between pH11 and pH 12.

In step 704, the extraction proceeded. The temperature of the extractionprocess was 30° C., and the duration of the extraction was 4 hours. Instep 705, the extraction slurry was filtered to remove residue withundissolved Psilocybe cubensis from the filtrate. The filtrate from thisstep was named filtrate A. In step 706, the residue was retained andplaced back in the extraction vessel. In step 707, another 5 L of thesame solvent was added to the residue. In step 708, the extractionprocess of the residue continued at a temperature of 30° C., for 4hours. The temperature remained constant during the extraction process.In step 709, the second extraction slurry was filtered to remove theresidue of unwanted solid material. Filtrates A and B were then mixed instep 710 to result in bulk filtrate C.

Bulk filtrate C was brought to a pH of 5 with 5M phosphoric acid in step711. The pH-adjusted concentrated slurry was processed with a rotaryevaporator in step 712 to remove solvent until the volume of filtrate Cwas 2.5 liters. At this point, the reduced amount of filtrate C was aconcentrated slurry, due to the precipitation of some of thepsychoactive alkaloids.

In step 713, the concentrated slurry was standardized. In this example,4.7 g of ascorbic acid, 1.9 g of SiO₂, and 47 g of maltodextrin wereadded to the concentrated slurry. In step 714, the standardizedconcentrated slurry was dried using a bench-top spray dryer. Thisresulted in 100 g of powdered psilocybin mushroom extract with a totalalkaloid concentration of 1.00% by weight.

Example 7: Extraction Using a Buffered Solvent Mixture of Ethanol andWater (3:1 wt %) (Acid Solvent)

Referring to FIG. 6 , a process is shown for the extraction ofpsychoactive compounds from Psilocybe cubensis mushrooms using abuffered acidic solvent. In step 600, 2.5 kg of raw psilocybin mushroomsfrom the Psilocybe cubensis species was provided. In step 601, the rawPsilocybe cubensis was dried in a forced air oven at 25° C. for 5-10hours. The dried biomass was 140 g. In step 602, the dried biomass wasground in a hammer mill or the equivalent, to particle size of 200 mesh.

In step 603, 5 L of solvent was added with the dried biomass to anextraction vessel, which was heat-controlled and agitated. The solventwas a pH-adjusted, hydro-ethanol mixture. For its preparation, 44 g ofanhydrous citric acid was placed into a 5 L vessel with 1.25 L ofreverse osmosis water followed by 3.75 L of ethanol. The contents weremixed until completely dissolved. The pH of this solution was between pH1.8 and pH 3.

In step 604, the extraction proceeded. The temperature of the extractionprocess was 30° C., and the duration of the extraction was 4 hours. Instep 605, the extraction slurry was filtered to remove residue withundissolved psilocybe cubensis from the filtrate. The filtrate from thisstep was named filtrate A. In step 606, the residue was retained andplaced back in the extraction vessel. In step 607, another 5 L of thesame solvent was added to the residue. In step 608, the extractionprocess of the residue continued at a temperature of 30° C., for 4hours. The temperature remained constant during the extraction process.In step 609, the second extraction slurry was filtered to remove theresidue of unwanted solid material. Filtrates A and B were then mixed instep 610 to result in bulk filtrate C.

Bulk filtrate C was brought to a pH of 5 with 5M sodium hydroxide instep 611. The amount of sodium hydroxide depends on the specificmushroom matrix extracted and was not possible to predict accurately.The pH-adjusted, concentrated slurry was then processed with a rotaryevaporator in step 612 to remove solvent until the volume of filtrate Cwas 2.5 liters. At this point, the reduced amount of filtrate C was aconcentrated slurry, due to the precipitation of some of thepsychoactive alkaloids.

In step 613, the concentrated slurry was standardized. In this example,4.7 g of ascorbic acid, 1.9 g of SiO₂, and 47 g of maltodextrin wereadded to the concentrated slurry. In step 614, the standardizedconcentrated slurry was dried using a bench-top spray dryer. Thisresulted in 100 g of powdered psilocybin mushroom extract with a totalalkaloid concentration of 1.00% by weight.

Example 8: Extraction Using 100% Methanol as a Solvent

Referring to FIG. 5 , a process is shown for the extraction ofpsychoactive compounds from Psilocybe cyanescens mushrooms using 100%methanol as the solvent.

In step 500, 2.5 kg of raw psilocybin mushrooms from the Psilocybecyanescens species was provided. In step 510, the raw Psilocybecyanescens was dried in a forced air oven at 25° C. for 10 hours. Thedried biomass was 140 g. In step 520, the dried biomass was ground in acutting mill or the equivalent, to particle size of 200 mesh. In step530, 5 kg of solvent, which was 100% methanol, was added to anextraction vessel, which was heat-controlled and agitated. The driesbiomass was also added to the extraction vessel.

In step 540, the extraction proceeded. The temperature of the extractionprocess was a constant 25° C., and the duration of the extraction was 4hours. A pressure of 100 kPa above atmospheric (15 psi) was applied tothe mixture of solvent and biomass during the extraction. In step 550,the extraction slurry was filtered to remove residue with undissolvedPsilocybe cyanescens from the filtrate.

The filtrate was then processed with a rotary evaporator in step 560 toevaporate all the methanol from the filtrate. In this embodiment, allthe solvent was removed at this stage because methanol was not regardedas safe for human consumption, and there should be no trace amounts ofit remaining in the final product. In step 570, 1.25 liters of reverseosmosis water at room temperature was added to the solid that isremaining after the evaporation step, to form a concentrated slurry.

In step 580, the concentrated slurry was standardized. In this example,1.84 g of SiO₂ and 46 g of maltodextrin were added to the concentratedslurry. In step 590, the standardized concentrated slurry was driedusing a bench-top spray dryer. This resulted in 95 g of powderedpsilocybin mushroom extract with a total alkaloid concentration of 1.50%by weight.

Example 9: Extraction Using 100% Water as a Solvent

Referring to FIG. 4 , a detailed process is shown for the extraction ofpsychoactive compounds Psilocybe cubensis using 100% reverse osmosiswater as the solvent.

In step 400, 2.5 kg of raw psilocybin mushrooms from the Psilocybecubensis species was provided. In step 401, the raw Psilocybe cubensiswas dried in a forced air oven at 25° C. for 10 hours. The dried biomasswas 140 g. Note that the dried biomass was the same weight in differentexamples because the mushrooms were from the same starting batch. Instep 402, the dried biomass was ground in a hammer mill or theequivalent, to a particle size of 200 mesh.

In step 403, 5 liters of solvent, which was 100% reverse osmosis water,was placed in an extraction vessel with the dried biomass, which washeat-controlled and agitated.

In step 404, the extraction proceeded. The temperature of the extractionprocess was 90° C., and the duration of the extraction was 12 hours. Inthe step 405, the extraction slurry was filtered while still hot toremove residue with undissolved Psilocybe cubensis from the filtrate.The filtrate from this step was considered as filtrate A. In step 406,the residue was retained and placed back in the extraction vessel. Instep 407, another 5 liters of 100% reverse osmosis water was added tothe residue. In step 408, the extraction process of the residuecontinued at a temperature of 90° C., for 10 hours. The temperatureremained constant during the extraction process. In step 409, the secondresulting mixture, of biomass solids and water with dissolved extract,was filtered while still hot to remove the residue of unwanted solidmaterial. Filtrates A and B are then mixed in step 410 to result in bulkfiltrate C.

The bulk filtrate C was then processed with a rotary evaporator in step411 to remove solvent until the volume of filtrate C is 2.5 liters. Atthis point, the reduced amount of filtrate C was a concentrated slurry,due to the precipitation of some of the psychoactive alkaloids.

In step 412, after some of the solvent has been removed using the rotaryevaporator, the concentrated slurry was then standardized. Thestandardization process used a titration procedure to determine theconcentration of the psychoactive alkaloids in the concentrated slurry.The standardization procedure entailed adjusting the concentration ofthe psychoactive alkaloids in the concentrated slurry to a desired drytarget. In this example, 6.3 g of ascorbic acid, 2.5 g of SiO₂ and 63 gof maltodextrin were added to the concentrated slurry.

In step 413, after the standardization process, the standardizedconcentrated slurry was dried using a bench-top spray dryer. Thisresulted in 140 g of powdered psilocybin mushroom extract with a totalalkaloid concentration of 0.50% by weight.

Example 10. Process with Prevention of Dephosphorylation

2.5 kg of Psilocybe cubensis were dried in a forced air oven at 25° C.for 10 hours to result in 140 g of dried biomass. The dried biomass wasthen pulverized to a size of 200 mesh with a mill.

A basified solvent, i.e. a pH-adjusted, hydro-ethanol mixture, wasprepared. 50 g of sodium hydroxide pellets were placed into a 5 L vesselwith 1.25 L of RO (reverse osmosis) water followed by addition of 3.75 Lof ethanol. The contents were mixed until completely dissolved. Abasified solvent with 75% EtOH v/v % and a pH of 13 was obtained.

The dried powdered biomass was placed into an agitated, heat-controlledvessel with 5 L of the basified solvent and mixed for extraction ofpsychoactive alkaloid. The extraction was controlled to a constant 75°C., and the time of extraction was 1 hour. The extraction slurry wasthen filtered. Filtration resulted in a filtrate, i.e. the psychoactivealkaloid liquid, and a filter residue. The filter residue was placedback into the extraction vessel and extracted with an additional 5 L ofthe basified solvent. The temperature of extraction was again 75° C. andthe time was again 1 hour. The resulting extraction slurry was thenfiltered. The filtrates from the first and second extractions were mixedto form 10 L of mixed filtrate. The pH of the mixed filtrate was thenreduced with 3 M citric acid until a pH of 4.5 was achieved. Immediatelyafter adjusting the pH, the mixed filtrate was placed into a rotaryevaporator at 50° C. and 250 torr, and the solvent was partially orcompletely evaporated to obtain a psychoactive alkaloid extract in aslurry or powdered form respectively. Final stages of evaporation wereperformed using a freeze dryer. When dried to a powder, the desiredamount of the phosphorylated psychoactive alkaloid obtained was 0.80% byweight (measured by HPLC analysis) in the psychoactive alkaloid extract.The desired amount of the dephosphorylated psychoactive alkaloidobtained was 0.05% by weight in the psychoactive alkaloid extract.

Example 11. Process for Heavily Phosphorylated Psychoactive AlkaloidComposition

The evaporation of the solvent from the mixed filtrate from Example 10was paused when the final volume of the filtrate was reduced to 2.5 L.The resulting slurry contained 236.9 mg/L psilocybin and 15.12 mg/Lpsilocin. The obtained psychoactive alkaloid slurry was standardized bythe addition of 38.64 g of maltodextrin, 1.12 g of ascorbic acid, and2.24 g of silicon dioxide. The standardization was followed by drying byfreeze drying to yield 112 g of the psychoactive alkaloid composition infree-flowing powder form. The composition had a psilocybin content of0.503% dry wt/wt % and a psilocin content of 0.003% dry wt/wt %.Further, the composition had a total phosphorylatable psychoactivealkaloid content of 0.506% dry wt/wt %.

Example 12. Process with Promotion of Dephosphorylation

2.5 kg of Psilocybe cubensis were dried in a forced air oven at 25° C.for 10 hours to result in 140 g of dried biomass. The dried biomass wasthen pulverized to a size of 200 mesh with a hammer mill.

An acidified solvent, i.e. a pH-adjusted, hydro-ethanol mixture, wasprepared. 144 g of anhydrous citric acid was placed into a 5 L vesselwith 1.25 L of RO water followed by the addition of 3.75 L of ethanol.The contents were mixed until completely dissolved. An acidified solventwith a pH of 2 was obtained.

The dried powdered biomass was placed into an agitated, heat-controlledvessel with 5 L of the acidified solvent and mixed for the extraction ofpsychoactive alkaloid. The extraction was controlled to a constant 75°C., and the duration of extraction was 1 hour. The extraction slurry wasthen filtered. Filtration resulted in a filtrate, i.e. the psychoactivealkaloid liquid, and a filter residue. The filter residue was placedback into the extraction vessel and extracted with an additional 5 L ofthe acidified solvent. The temperature of extraction was again 75° C.and the time was 1 hour. The extraction slurry was filtered. Thefiltrates from the first and second extraction were mixed to form 10 Lof mixed filtrate. The pH of the mixed filtrate was then increased with5 M sodium hydroxide until a pH of 4.5 was achieved. Immediately afteradjusting the pH, the mixed filtrate was placed into a roto-evaporatorat 50° C. and 250 torr, and the solvent was partially or completelyevaporated to obtain a psychoactive alkaloid extract. Final stages ofevaporation were performed using a freeze dryer. When dried to a powder,the desired amount of the phosphorylated psychoactive alkaloid obtainedwas 0.00% by weight in the psychoactive alkaloid extract. The desiredamount of the dephosphorylated psychoactive alkaloid obtained was 0.86%by weight in the psychoactive alkaloid extract.

Example 13. Process for Preparation of a Psychoactive AlkaloidComposition

The evaporation of the solvent from the mixed filtrate from Example 12was paused until the final volume of the filtrate was reduced to 2.5 L.The obtained psychoactive alkaloid slurry had a 241.85 mg/L of psilocinand a 0 mg/L of psilocybin. The slurry was standardized by the additionof 47.07 g of maltodextrin, 1.21 g of ascorbic acid, and 2.41 g ofsilicon dioxide. The standardization was followed by freeze drying toyield 120.7 g of the psychoactive alkaloid composition in free-flowingpowder form. The composition had a psilocybin content of 0.00% dry wt/wt% and a psilocin content of 0.501% dry wt/wt %. Further, the compositionhad a total phosphorylatable psychoactive alkaloid content of 0.501% drywt/wt %.

Example 14. Process for Preparation of a Psychoactive AlkaloidComposition Containing a Mixture of Phosphorylated and DephosphorylatedAlkaloids

In an alternate method, the slurry from Examples 12 and 13 can becombined to form 5 L of slurry containing 118.45 mg/L of psilocybin and128.49 mg/L of psilocin. The slurry was standardized by the addition of85.70 g of maltodextrin, 2.33 g of ascorbic acid, and 4.65 g of silicondioxide. The standardization was followed by lyophilization to yield232.70 g of the psychoactive alkaloid composition in the free-flowingpowder form. The composition had a psilocybin content of 0.255% drywt/wt % and a psilocin content of 0.276% dry wt/wt %. Further, thecomposition had a total phosphorylatable psychoactive alkaloid contentof 0.502% dry wt/wt %.

Example 15: Purifying the Psychoactive Alkaloid Extract Using aNon-Ionic Macroporous Resin

The pH of the partially concentrated extract of Example 1, which was anaqueous extract, was adjusted to pH 4.0 (+/−0.5) by adding 2 Mphosphoric acid and centrifuged for 15 minutes at 3000 g to remove anysolid precipitate. The pH of 4 corresponds to the isoelectric point ofpsilocybin, and psilocin's polarity is such that it is partitioned ontothe resin, thus allowing effective binding of the psychoactive alkaloidspsilocybin and psilocin to the macroporous resin. Norbaeocystin andbaeocystin are phosphorylated and behave in the same way as psilocybin.The supernatant obtained was loaded onto a column of Amberlite® XAD4, anon-ionic macroporous resin (50.34 g of dry resin) at a flow rate of 2bed volumes per hour, to allow components in the supernatant to beadsorbed onto the macroporous resin. After all 2.5 L of the extract wasloaded onto the column of macroporous resin, the column was washed in asingle pass with 5 bed volumes of reverse osmosis water at roomtemperature. This was followed by elution with 5 bed volumes of 5%ethanol (by weight), again at room temperature. Finally, the column waswashed in a single pass with 5 bed volumes of 100% ethanol. The elutionwas performed at room temperature. Each of these three fractions wascollected separately. The particular order for the washing steps and theelution was selected to be in the order of the polarity of the solvents.If the order were different, an inferior result may have ensued, such asa lower yield. The first fraction using reverse osmosis water removedthe most polar compounds from the resin. The hydro-ethanol fractioneluted compounds of lesser polarity, and the 100% ethanol solventremoved the least polar compounds. Less polar solvents could also beused to elute less polar compounds.

The 5% ethanol fraction (i.e. the purified psychoactive alkaloidsolution) was then concentrated in a rotary evaporator to form 3.90 g ofconcentrated aqueous slurry at 30% solids, containing 195.1 mg of totalalkaloids, i.e. psilocybin, psilocin, norbaeocystin, and baeocystin. Theresult was a purified psychoactive alkaloid slurry having a totalpsychoactive alkaloid concentration of 5.00% by weight.

As described below, it is possible to replace the solvent with anequivalent weight of excipients to provide a purified extract with apsychoactive alkaloid content of 5.00% dry wt/wt %.

Example 16: Purifying the Psychoactive Alkaloid Extract Using CationExchange and Non-Ionic Macroporous Resins

The combination of filtrates of Example 11 was taken as the startingpoint. The pH of the combined filtrate obtained was adjusted to a pH of3.0 (+/−0.5) by adding 1M HCl. It was then mixed with 200 g ofAmberlite® MAC-3 H, a strong cationic ion-exchange resin in its hydrogenform, to result in a filtrate-resin mixture, in which components of thepsychoactive alkaloid filtrate were adsorbed onto the cation exchangeresin. The pH of 3 ensured that the psychoactive alkaloid (i.e.psilocybin) was in its protonated form, and thus adsorbed onto thecationic exchange resin efficiently. The filtrate-resin mixture wasagitated for 4 hours at room temperature (21° C.-25° C.) and thenfiltered. The filtrate was discarded, and the resin was rinsed with 2.0L of 100% EtOH and then 2.0 L of H₂O to remove any impurities. Finally,the psilocybin/psilocin fraction was eluted with 2.0 L of 2% HCl/80%EtOH, for 4 hours at room temperature.

The eluted fraction was brought to a pH of 4.0 (i.e. the isoelectricpoint of psilocybin) by adding 2M NaOH. The filtrate was thencentrifuged at 3000 g to remove any solid precipitate. The resultantfiltrate, in form of an aqueous solution, was then placed into a rotaryevaporator and the solvent was removed until the aqueous solutionreached a volume of 400 mL. The aqueous solution was then againcentrifuged for 15 minutes at 3000 g to remove any solid precipitate.The supernatant was loaded onto a column of Amberlite® XAD4 macroporousresin (45.53 g of dry resin) at a flow rate of 2 bed volumes per hour.After all the 400 mL of the supernatant was loaded onto the column, itwas initially washed with 5 bed volumes of reverse osmosis water,followed by elution with 5 bed volumes of 5% ethanol (by weight) andthen washed with 100% ethanol. Each of these fractions was collectedseparately. The 5% ethanol fraction (i.e. the purified psychoactivealkaloid solution) was concentrated in a rotary evaporator to form 258mg of solution containing 175 mg of total alkaloids (i.e. psilocybin,psilocin, norbaeocystin, and baeocystin). Thus, a purified psychoactivealkaloid slurry with a total alkaloid concentration of 68% dry wt/wt %was obtained.

Example 17: Purifying the Psychoactive Alkaloid Extract Using AnionExchange and Non-Ionic Macroporous Resins

The combination of filtrates of Example 11 was taken as the startingpoint. The pH of the filtrate combination was adjusted to 9.5 (+/−0.5)by adding 1 M NaOH and then mixed with 150 g of Amberchrom® 50WX8 stronganionic ion-exchange resin in its hydrogen form to result in afiltrate-resin mixture, in which components of the psychoactive alkaloidfiltrate were adsorbed onto the anion exchange resin. The pH of 9.5(+/−0.5) ensured that the psilocybin, psilocin, norbaeocystin, andbaeocystin were deprotonated and had a net negative charge for efficientadsorption onto the strong anion exchanger.

The filtrate-resin mixture was agitated for 4 hours and then filteredout, and the filtrate was discarded. The resin was rinsed with 2.0 L of100% EtOH and then 2.0 L of H₂O to remove impurities. Finally, thepsilocybin/psilocin fraction was eluted with 2.0 L of 2% NaCl/80% EtOHfor 4 hours.

The eluted fraction was brought to a pH of 4.0 with the addition 2 MHCl. The extract was then centrifuged at 3000 g to remove any solidprecipitate. The resultant extract, in from of a solution, was thenplaced into a rotary evaporator and the solvent was removed to result ina volume of 400 mL.

The resultant 400 mL aqueous solution was centrifuged for 15 minutes at3000 g to remove any solid precipitate. The supernatant was loaded ontoa column of Amberlite® XAD4 macroporous resin (45.53 g of dry resin) ata flow rate of 2 bed volumes per hour, to allow components of thesupernatant to be adsorbed onto the macroporous resin. After all 400 mLof supernatant was loaded onto the column, the column was initiallywashed with 5 bed volumes of reverse osmosis water, followed by elutionwith 5 bed volumes of 5% ethanol (by weight) and then a final wash with100% ethanol was performed. Each of these fractions was collectedseparately. The 5% ethanol fraction (i.e. the purified psychoactivealkaloid solution) was concentrated in a rotary evaporator to form 325mg of solution containing 175 mg of total alkaloids (i.e. psilocybin,psilocin, norbaeocystin, and baeocystin). A purified psychoactivealkaloid slurry with a concentration of 54% dry wt/wt % of totalalkaloids was therefore obtained.

Example 18: Purifying the Anadenanthera peregrina Seed Extract

The aqueous extract with about 6.8% solids, from Example 17, wasadjusted to pH 4.0 (+/−0.5) with 2 M phosphoric acid and centrifuged for15 minutes at 3000 g to remove any solid precipitate. The supernatantwas loaded onto a column of Seplite® LXA17 macroporous resin (54.21 g ofdry resin) at a flow rate of 2 bed volumes per hour. After all 6.0 L ofthe extract was loaded onto the column, it was initially washed with 5bed volumes of reverse osmosis water, followed by a second wash with 5bed volumes of 10% ethanol (by weight) and then eluted with 3 bedvolumes of 50% ethanol, and finally the resin was washed with 5 bedvolumes of 100% ethanol. Fewer bed volumes of solvent were possible inthe elution step than in the washing steps due to the sharper elutionpeak. This in turn led to a shorter evaporation time than if more bedvolumes of the solvent had been used. Each of these fractions wascollected separately. The 50% ethanol fraction was concentrated in arotary evaporator to form 355 g of concentrated aqueous slurry at 30%solids, containing 3.03 g of total alkaloids.

Example 19: Process for Preparing Standardized Psychoactive AlkaloidExtract

The 3.90 g of purified psychoactive alkaloid slurry with a psychoactivealkaloid concentration of 5.00% by weight that was obtained in Example15 was taken and standardized. To achieve this, the concentrated slurry,0.03 g of SiO₂, 0.02 g of ascorbic acid and 2.55 g of maltodextrin wereadded and thoroughly mixed to result in a final standardized slurryhaving a specific concentration of alkaloids. The final standardizedslurry was then subjected to spray-drying and a final powdered alkaloidextract with a 5.00% total psilocybin, psilocin, baeocystin andnorbaeocystin concentration by dry weight was obtained.

Example 20: Process for Preparing Standardized Psychoactive AlkaloidExtract from Anadenanthera peregrina Seeds

The aqueous slurry from Example 18 was used as the starting point. Next,0.3 g of SiO₂, 0.15 g of citric acid and 4.10 g of maltodextrin wereadded to the slurry, which was thoroughly mixed. The final formulatedslurry was then subjected to spray-drying to yield a final powderedalkaloid extract with a combined bufotenin/bufotenidine/5-MeO-DMTconcentration of 20.00% by dry weight.

Example 21: Preparation of a Non-Purified Psychoactive Alkaloid Extract

Fresh Psilocybe cubensis, 2.5 kg, was dried in a forced air oven at 25°C. for 5-10 hours, to result in 140 g of dried biomass. The driedbiomass was pulverized to a size of 200 mesh with a hammer mill. Thedried powdered biomass was then placed into an agitated, heat-controlledvessel with 5 kg of solvent. The solvent was a hydro-ethanol mixture of3 parts ethanol to 1 part water by weight. The extraction was controlledto a constant 70° C., and the time of extraction was 4 hours.

The extraction slurry was filtered while hot, and the filter residue wasplaced back into the extraction vessel, and extracted with an additional5 kg of 3:1 ethanol:water mixture by weight. The temperature ofextraction was again 70° C., and the time was 4 hours. The extractionslurry was filtered while hot and the filtrates from the first andsecond extractions were mixed together to obtain a bulk filtrate. Thebulk filtrate was immediately placed into a rotary evaporator, and thesolvent was concentrated in the rotary evaporator to obtain 186.6 g ofthe psychoactive alkaloid extract in form of a concentrated aqueousslurry at 30% solids, containing 700 mg of total alkaloids, which wouldbe a concentration of 1.25% dry wt/wt %, if the slurry were to be dried.

Example 22: Preparation of a Purified Psychoactive Alkaloid Extract

Fresh Psilocybe cubensis, 2.5 kg, was dried in a forced air oven at 25°C. for 5-10 hours, resulting in 140 g of dried biomass. The driedbiomass was then pulverized to a size of 200 mesh with a hammer mill.The dried powdered biomass was placed into an agitated, heat-controlledvessel with 5 kg of solvent. The solvent used was a hydro-ethanolmixture of 3 parts ethanol to 1 part water by weight. The extraction wascontrolled to a constant 70° C., and the time of extraction was 4 hours.

The extraction slurry was filtered while hot, and the filter residue wasplaced back into the extraction vessel, and extracted with an additional5 kg of 3:1 ethanol:water mixture by weight. The temperature ofextraction was again 70° C. and the time was 4 hours. The extractionslurry was filtered while hot and the filtrates from the first andsecond extractions were mixed together to obtain a bulk filtrate. Thebulk filtrate was left to cool, in case any precipitate had formed, theinsoluble material was filtered out and discarded.

The bulk filtrate's pH was then adjusted to 9.5 (+/−0.5) with 1 M NaOHto form a specific pH psychoactive alkaloid solution. This solution wasthen mixed with 150 g of Amberchrom® 50WX8 Strong Anion Exchange resinin its hydrogen form. The solution was agitated for 4 hours and thenfiltered. The filtrate was discarded. The resin was rinsed with 2.0 L of100% EtOH and then 2.0 L of H₂O. Finally, the psilocybin fraction waseluted with 2.0 L of 2% NaCl/80% EtOH for 4 hours.

The eluted fraction was brought to a pH of 4.0 with 2 M HCl to result inanother specific pH psychoactive alkaloid solution. This solution wasthen centrifuged at 3000 g to remove any solid precipitates. The solventfrom the solution was then evaporated in a rotary evaporator to resultin a volume of solvent evaporated was 400 m L.

This solution was again centrifuged for 15 minutes at 3000 g to removeany solid precipitate. The supernatant was loaded onto a column ofAmberlite® XAD4 macroporous resin (45.53 g of dry resin) at a flow rateof 2 bed volumes per hour. All 400 mL of the extract was loaded onto thecolumn and washed with 5 bed volumes of reverse osmosis water. Thewashing step was followed by elution with 5 bed volumes with 5% ethanol(by weight). A final washing was carried out with 100% ethanol. Each ofthese fractions was collected separately. The 5% ethanol fraction wascollected and concentrated in a rotary evaporator to obtain 1.143 g of30% liquid slurry containing 175 mg of total alkaloids, a concentrationof 54% dry wt/wt %.

Example 23: Preparation of a Psychoactive Alkaloid Composition with aNon-Purified Psychoactive Alkaloid Extract

The psychoactive alkaloid extract obtained in Example 12 was mixed with2.8 g of silicon dioxide (flow agent), 0.140 g of ascorbic acid(preservative), and 81.06 g of tapioca maltodextrin (carrier). The finalformulated slurry was then subjected to spray-drying and 140 g of thestandardized powdered composition was produced with the desired specificamount of psychoactive alkaloid. The total psilocybin/psilocinconcentration by dry weight was 0.5% in this composition. The exactweight percentages of the components in the composition are depictedTable 1.

Example 24: Preparation of a Psychoactive Alkaloid Composition with aPurified Psychoactive Alkaloid Extract

The purified psychoactive alkaloid extract obtained in Example 22 wasmixed with 5.85 mg of ascorbic acid (preservative) and 822 mg of ricemaltodextrin (carrier). The final formulated slurry was then subjectedto lyophilization and 1.171 g of the standardized powdered compositionwas produced. The total psilocybin/psilocin concentration by dry weightwas 15.01% in the composition. The exact weight percentages of thecomponents in the composition are depicted Table 1.

Example 25: Process for Preparing Standardized Psychoactive AlkaloidExtract

A purified psychoactive alkaloid solution resulting from resin treatmentafter extraction from 140 g of dried Psilocybe cubensis was concentratedin a rotary evaporator to form 3.90 g of concentrated aqueous slurry at30% solids, containing 195.1 mg of total psychoactive alkaloids. Theslurry, with a psychoactive alkaloid concentration of 5.00% by weight,was mixed with 0.03 g of SiO₂, 0.02 g of ascorbic acid and 2.55 g ofmaltodextrin. This standardized slurry was then subjected tospray-drying, and a final powdered alkaloid extract with a 5.00% totalpsilocybin, psilocin, baeocystin and norbaeocystin concentration by dryweight was obtained.

Example 26: Process for Preparing Standardized Psychoactive AlkaloidExtract

An extract from 140 g dried Psilocybe cubensis mushrooms using a 75%ethanol solvent resulted in a concentrated slurry, for which thealkaloid content was 2.16 g and the total solid content was 46.4 g. Tothe slurry, 4.7 g of ascorbic acid, 1.9 g of SiO₂ and 47 g ofmaltodextrin were added. After spray drying, this resulted in 100 g ofpowdered psychedelic mushroom extract with a total alkaloidconcentration of 1.00% by weight.

Example 27: Process for Preparing Standardized Psychoactive AlkaloidExtract

Psychoactive compounds were extracted from 140 g of dried Psilocybecubensis using 100% reverse osmosis water as the solvent. Water wasevaporated to result in a concentrated slurry, for which the alkaloidcontent was 1.82 g and the total solid content was 68.18 g. In thisexample, 6.3 g of ascorbic acid, 2.5 g of SiO₂ and 63 g of maltodextrinare added to the concentrated slurry, which was then dried. Thisresulted in 140 g of powdered psilocybin mushroom extract with a totalalkaloid concentration of 0.50% by weight.

Example 28: Process for Preparing Standardized Psychoactive AlkaloidExtract

An extraction of psychoactive compounds from 140 g dried Psilocybecyanescens mushrooms was performed using 100% methanol as the solvent.The extraction slurry was filtered to remove residue with undissolvedPsilocybe cyanescens from the filtrate. All the methanol was evaporatedfrom the filtrate, then 1.25 liters of reverse osmosis water at roomtemperature was added to the remaining solid to form a slurry, for whichthe alkaloid content was 2.87 g and total solid content was 47.14 g.Next, 1.84 g of SiO₂ and 46 g of maltodextrin were added to the slurry,which was then dried. This resulted in 95 g of powdered psychedelicmushroom extract with a total alkaloid concentration of 1.50% by weight.

Example 29-3.7: Process for Preparing Standardized Psychoactive AlkaloidExtract

An extract obtained according to Example 22 was used as the startingpoint. Compared to Example 24, greater amounts of preservative (351 mg),flow agent (351 mg) and carrier (16.515 g) were added to thecomposition. This resulted in a standardization of the amountpsychoactive alkaloid in the composition to 1.00% instead of 15.01%.

Example 30: Process for Preparing Standardized Psychoactive AlkaloidExtract

A purified psychoactive alkaloid solution resulting from resin treatmentafter extraction from 140 g of dried Psilocybe cubensis was concentratedin a rotary evaporator to form 3.90 g of concentrated aqueous slurry at30% solids, containing 195.1 mg of total psychoactive alkaloids.Compared to Example 25, greater amounts of preservative (0.49 g), flowagent (0.39 g), and carrier (18.43 g) were added to the composition.This resulted in a standardization of the amount psychoactive alkaloidin the composition to 1.00% instead of 5.00%.

Example 31: Process for Preparing Standardized Psychoactive AlkaloidExtract

A purified psychoactive alkaloid solution was obtained after multiplecation exchange resin treatments following extraction from 140 g ofdried Psilocybe cubensis. Silicon dioxide, maltodextrin and ascorbicacid were added to form a composition standardized to 60.00%.

Example 32: Process for Preparing Standardized Psychoactive AlkaloidExtract

This is as Example 31, except that the only excipient that was added waspreservative (ascorbic acid). This resulted in a standardization of thepsychoactive alkaloid content of the composition to 75.00%.

The exemplary compositions obtained are depicted in Table 1.Compositions of Examples 23 and 26-28 are compositions with apsychoactive alkaloid extract that has not been purified. Compositionsof Examples 24, 25, and 29-32 are compositions with a purifiedpsychoactive alkaloid extract.

TABLE 1 Compositions of Examples 23-32 Alkaloid Alkaloid Amount inExtract Preservative Flow Agent Carrier Total Amount in StandardizedMass Mass Mass Mass Mass Extract Composition Ex. (dry %) (dry %) (dry %)(dry %) (dry %) (wt/wt %) (wt/wt %) 23 40.0 0.1 2.0 57.9 100.0 1.25 0.5024 29.3 0.5 0.0 70.2 100.0 51.23 15.01 25 31.0 0.5 0.8 67.6 100.0 16.125.00 26 46.4 4.7 1.9 47.0 100.0 2.16 1.00 27 48.7 4.5 1.8 45.0 100.01.03 0.50 28 49.6 0.0 1.9 48.4 100.0 3.02 1.50 29 2.0 2.0 2.0 94.0 100.051.23 1.00 30 6.2 2.5 2.0 89.3 100.0 16.12 1.00 31 79.6 5.0 1.0 14.4100.0 75.22 60.00 32 99.7 0.3 0.0 0.0 100.0 75.22 75.00

In the columns, the extract mass (dry %), preservative mass (dry %),flow agent mass (dry %), and carrier mass (dry %) are the dry weightpercentages of the psychoactive alkaloid extract, preservative, flowagent and carrier in the standardized composition respectively. Thetotal mass (dry %) is the total dry weight percentage of thestandardized composition. The alkaloid amount in the extract (wt/wt %)is the dry weight percentage of the psychoactive alkaloid in theextract, as if the extract were in its dried state. Note that it ispossible for the extract to remain in the slurry state as the excipientsare added. The alkaloid amount in the standardized composition (wt/wt %)is the dry weight percentage of the psychoactive alkaloid in the finalcomposition. It can be seen that a wide variability in extractconcentration from different batches can be standardized to the sameconcentration in the composition, e.g., by looking at examples 26, 29,and 30.

Example 33: 95% Methanol/5% Acetic Acid (Psilocybin-Rich Extract)

14.5 kg of fresh Psilocybe cubensis were dried in a forced air oven at30° C. for 48 hours, resulting in 1.45 kg of dried biomass mushroomfruiting body. The content of psilocybin in the biomass was 0.523% bydry weight, resulting in 7.25 g of psilocybin available for extraction.The dried biomass was reduced to a size of 200 mesh with a cutting mill.The dried powdered biomass was placed into an agitated, heat-controlledvessel with 58 L of solvent (40 L/kg). FIG. 24 shows a chart for solventto solid ratio optimization. A S:S (solvent:solid) ratio of 20-30 L/kgcan achieve >90% alkaloid yield over 3 extractions while the optimalcondition was chosen as 40-50 L/kg, achieving >90% alkaloid yield inonly two extractions, reducing the amount of solvent waste, time, andenergy during the evaporation step. In this embodiment, the solvent wasacidified methanol (5% acetic acid/95% anhydrous methanol v/v %). It isnoteworthy that methanol works very well, and acidified methanol works10-15% better. Both are acceptable extraction methods for psilocybin.The extraction was controlled to a constant 25° C. temperature and wasunder atmospheric pressure. The extraction was carried out under theseconditions for 30 minutes, after which the extraction slurry wasfiltered through a 5 μm stainless steel filter. The filtrate was placedinto another vessel and put aside. FIG. 25 shows a graph of time andtemperature optimization, which indicates that the temperature increasesthe extraction efficiency, but also shows degradation when extendedbeyond 20-30 minutes. Given that, at scale, the increased complexity ofelevating the temperature of the extraction vessel would introduce asignificant warming and cooling time, it was decided to select theextraction temperature of 20° C., and keep the extended extraction timeat 30-50 minutes to avoid degradation of the alkaloids. The now-dryfilter cake was again placed into the extraction vessel and anadditional 58 liters of extraction solvent was added to the vessel. Theextraction was again carried out under the same conditions for 30minutes. The slurry was then filtered and combined to create the pooledfiltrate. The pooled filtrate was placed into a rotary-evaporator, andthe methanol was evaporated until the volume was reduced to around 5.8L, forming a concentrated solution. 5.8 L was roughly 5% of the pooledfiltrate volume, which was entirely acetic acid at this point and aroundpH 2.4. Basically, it is required to remove all of the methanol forfurther purification. It may be also possible to take this solution andevaporate it fully to dryness, add excipient and have a shelf-stable lowpurity extract (0.5-2.0% alkaloid content by weight). It is possible tohave this material continue onto purification. The content of psilocybinin this concentrated solution was 1.18 g/L, and the yield was 94.2%. Thedry mass yield at this stage was 44.23%. Components that are stillpresent in the extract at this point are: small chaincarbohydrates/polysaccharides, free sugars, polyphenols, alkaloids, someglycoproteins, ergothioneine, tocopherols, ergosterols, fats. Many ofthese components are targeted for removal with purification. Componentsthat are present in the mushroom that are left behind in the biomass:proteins, large carbohydrates/polysaccharides, B-glucans.

The concentrated solution was diluted with RO water to 50 L (1.28% drymass concentration). The aqueous extract was then adjusted to pH 4.0(+/−0.5) with 2 M sodium hydroxide and filtered through a 5 μm stainlesssteel filter to remove any solid precipitate. It is very important tohave the extract be at pH 4.0 before application to the adsorbent resin,because pH 4 is the isoelectric point of psilocybin, and it is also themaximum stability pH for psilocin. The supernatant was loaded onto acolumn of Amberlite® XAD4 macroporous resin (5000 mL of hydrated resin,˜1.39 mg psilocybin/mL of hydrated resin) at a flow rate of 2 bedvolumes per hour. Optimization of breakthrough and determination ofcapacity is shown in FIG. 26 (see also Table 2). After all 50 L ofextract is loaded onto the column, it was washed with 3 bed volumes ofreverse osmosis water at a flow rate of 2 BV/h, followed by elution with5 bed volumes of 15% ethanol (by weight) and then finally washed with100% ethanol. Each of these fractions was collected separately. FIG. 27shows a graph of optimized recovery of psilocybin on XAD4 with 1 pass.Desorption with 15% ethanol resulted in 99.2% recovery of psilocybinwhile retaining only 2.5% of the dry mass in the same fraction. Thisresulted in a ˜40× increase in concentration over the extract and a 45%dry wt/wt % content of psilocybin in the first pass purified extract. Inone embodiment, it is preferred to stop here and bring in the excipientsfor stabilization and standardization to a dry powder. If it is intendedto go higher and purer, it is preferred to expose the concentratedextract to another pass on the XAD4 or to an Isolute® SCX resin orantisolvent addition, or liquid/liquid extraction. The 15% ethanolfraction contained 6.79 g of psilocybin and 16.03 g of dry mass,resulting in an extract of 42.35% psilocybin by weight. The 15% ethanolfraction was then concentrated in a rotary evaporator to form 53.45 g ofconcentrated aqueous slurry at 30% solids.

1.09 g of SiO₂, 1.36 g of ascorbic acid, 1.36 g of citric acid, 17.24 gof maltodextrin, and 17.24 g of mannitol were added to the concentratedaqueous slurry, and it was thoroughly mixed. The final formulated slurrywas then subjected to lyophilization, and the final powdered alkaloidextract concentration was 12.5% total psilocybin concentration and lessthan 0.4% psilocin by dry weight. SiO₂ and maltodextrin were added asflowability enhancers. Mannitol is a cryoprotectant (allowing forefficient freeze-drying) and bulking agent. Ascorbic acid is anantioxidant (allowing protection from oxidation by first oxidizingitself), and citric acid is a chelating agent that may impart increasedbioavailability and pH buffering once inside the stomach. Thiscomposition has been developed and has shown 9 months of shelf stability(see Table 3).

TABLE 2 XAD4 Psilocybin Capacity at Three Different Flow Rates 2 BV/h 4BV/h 6 BV/h Capacity (mg Alkaloids) 765 mg 600 mg 463 mg mL Resin 550550 550 mg Alkaloids/mL XAD4 1.39 1.09 0.84

TABLE 3 Individual Time-Point Data of Psilocybin, Psilocin and MoistureContent of PYEX-FP-200820 Psilocybin Psilocin Moisture Content Months(wt/wt %) (wt/wt %) (%) 0 13.99 ± 0.12 0.91 ± 0.02 7.23 1 13.89 ± 0.110.90 ± 0.02 6.94 2 14.00 ± 0.19 0.91 ± 0.02 6.77 3 13.91 ± 0.28 0.92 ±0.03 6.93 4 13.81 ± 0.22 0.92 ± 0.02 7.14 5 13.86 ± 0.10 0.92 ± 0.047.22 6 13.89 ± 0.07 0.92 ± 0.04 6.87 7 13.95 ± 0.09 0.93 ± 0.03 6.9 813.85 ± 0.16 0.96 ± 0.02 7.31 9 13.93 ± 0.17 0.93 ± 0.04 6.93

Example 34: 0.15 M Citric Acid/Water (Psilocin Extract)

15.7 kg of fresh Psilocybe cubensis mushrooms were dried in a forced airoven at 30° C. for 48 hours, resulting in 1.57 kg of dried biomassmushroom fruiting body. The content of psilocybin in the biomass was0.523% by dry weight, resulting in 8.21 g of psilocybin available toconvert to 5.90 g psilocin (stoichiometrically). The dried biomass wasreduced to a size of 200 mesh with a cutting mill. The dried powderedbiomass was placed into an agitated, heat-controlled vessel with 78.5 Lof solvent (50 L/kg). FIG. 29 shows a chart of solvent to solid ratiooptimization for water. The optimal is 50 L/kg which was the lowest S:Sratio that can obtain >90% psilocin yield in two extractions. In thisembodiment, the solvent was acidified water (0.15 M citric acid, pH2.0). The extraction was controlled to a constant 25° C. temperature andwas under atmospheric pressure. The extraction was carried out underthese conditions for 60 minutes, and the extraction slurry was filteredthrough a 5 μm stainless steel filter. The filtrate was placed intoanother vessel and put aside. The now-dry filter cake was again placedinto the extraction vessel, and an additional 78.5 L of extractionsolvent was added to the vessel. The extraction was again carried outunder the same conditions for 60 minutes. The slurry was then filteredand combined to create the pooled filtrate. The pooled filtrate had acontent of psilocin of 0.034 g/L, and the yield was 91.23%. The dry massyield at this stage was 68.92%. The dry mass yield was so high becauseof the citric acid content.

The filtrate was directly loaded onto a column of Amberlite™ XAD4macroporous resin (2700 mL of hydrated resin, ˜1.98 mg psilocin/mL ofhydrated resin) at a flow rate of 2 bed volumes per hour (FIG. 30 ).

After all 157 L of extract was loaded onto the column, it was washedwith 3 bed volumes of reverse osmosis water at a flow rate of 2 BV/h,followed by elution with 5 bed volumes of 15% ethanol (by weight) andthen finally washed with 100% ethanol. Each of these fractions wascollected separately. The 15% ethanol fraction contained 5.11 g ofpsilocin and 14.94 g of dry mass, resulting in an extract of 34.20%psilocin by weight. The 15% ethanol fraction was then concentrated in arotary evaporator to form 49.80 g of concentrated aqueous slurry at 30%solids.

0.82 g of SiO₂, 1.64 g of ascorbic acid, 0.41 g of citric acid, 11.54 gof potato starch, and 11.54 g of mannitol was added to the slurry andthoroughly mixed. The final formulated slurry was then subjected tolyophilization, and the final powdered alkaloid extract concentrationwas 12.5% total psilocin concentration and no psilocybin was present inthe formulation.

TABLE 4 XAD4 psilocybin capacity at three different flow rates 2 BV/h 4BV/h 6 BV/h Capacity (mg Alkaloids) 811 mg 678 mg 595 mg mL Resin 410550 550 mg Alkaloids/mL XAD4 1.98 1.65 1.45

Example 35. Psilocybe CUBENSIS Extraction, Purification, andStabilization Rationale

The indole alkaloids present in Psilocybe mushrooms can be separatedinto two categories, the phosphorylated pro-drugs (psilocybin,norbaeocystin, baeocystin and aeruginascin) and their dephosphorylatedactive constituents (psilocin, 4-hydroxytryptamine, norpsilocin and4-hydroxy-N,N,N-trimethyltryptamine respectively). When these moleculesare consumed (whether in the raw mushroom, purified extracts, orsynthetic preparations of the compounds) the phosphorylated analoguesare enzymatically metabolized by the human gut, liver, and kidneys tothe active dephosphorylated forms. When considering a standardizedextract composition, there are benefits to controlling whether theextraction conditions will favor producing the dephosphorylated orphosphorylated forms.

The dephosphorylated indole alkaloids are well known to be unstable.Internal experiments have also quantified and substantiated thesefindings under aqueous conditions across the pH spectrum (Tables 5 and6).

TABLE 5 pH Stability of purified psilocybin over time. Recovery (%)Psilocybin T = 0 T = 4 h T = 16 h pH 1 98.43 97.23 96.32 pH 2 97.5695.72 95.64 pH 3 90.46 102.32 102.08 pH 4 95.60 102.69 102.20 pH 5 94.0193.89 93.23 pH 6 103.30 102.30 101.09 pH 7 95.72 100.21 98.90 pH 8 98.4198.44 97.31 pH 9 97.92 95.67 95.46 pH 10 102.32 103.19 102.60 pH 11105.36 105.50 104.66 pH 12 100.66 100.24 96.33

TABLE 6 pH Stability of purified psilocin over time. Recovery (%)Psilocin T = 0 T = 4 h T = 16 h pH 2 102.75 77.06 57.60 pH 3 90.63 90.8372.02 pH 4 93.58 99.08 81.47 pH 5 84.40 69.27 59.45 pH 6 95.41 74.2262.66 pH 7 96.33 74.40 46.72 pH 8 90.83 74.40 46.62 pH 9 76.07 43.490.00 pH 10 88.99 42.39 20.46 pH 11 86.24 39.17 0.00 pH 12 88.07 22.2910.37

While the dephosphorylation reaction is inevitable when consumed byhumans, it also happens rapidly within the Psilocybe mushroomsthemselves as a defense mechanism. The “bluing reaction” that occurswhen the fresh mushrooms are bruised (while harvesting or handling) is aresult of enzymatic dephosphorylation of psilocybin to psilocin,followed by enzymatic oxidation and dimerization of psilocin tosemiquinoid dimers and polymers (FIG. 32A) (Lenz 2020). In the presentdisclosure, a method that either promotes or inhibits various steps ofthis degradation cascade and uses them has been developed to beadvantageous during the extraction of indole alkaloids from psilocybemushrooms.

Psilocybin and psilocin are soluble in methanol and water and are notsoluble in isopropanol, ethanol and acetone. Experiments were performedto determine the best solvent compositions for extraction (FIGS. 32B and32C; Table 7)

TABLE 7 Dry weight concentration of each extract produced from eachcomposition (dried) wt/wt % Alkaloid Concentration in Dry Extract %Solvent Methanol Ethanol Isopropanol Acetone 0 0.066 0.066 0.066 0.06620 0.131 0.190 0.180 0.060 40 0.184 0.233 0.586 0.075 60 0.765 1.0310.966 0.068 80 0.836 1.283 1.233 0.000 100 1.313 0.399 0.780 0.000

Methanol was shown to be the superior solvent of choice for extractingthese alkaloids in general; the optimal composition was 100% anhydrousmethanol which resulted in a near 100% extracted yield of psilocybin andpsilocin. Any percentage of water in the extraction was shown todecrease yield of both analytes, indicating that the mushroom biomassshould be as dry as possible so as to introduce a minimal amount ofwater. It is likely that any amount of water present in the extractionsolvent allows phosphatase to act upon the phosphorylated alkaloids,converting them to their dephosphorylated counterparts. In the solventcompositions that have low total yield, laccase enzyme is also activelyoxidizing psilocin to their semiquinoid breakdown products.

80% ethanol was also an effective solvent, however, it was observed thatwhile the total alkaloid yield was high (>90%), some psilocybin wasconverted to psilocin during the extraction.

Since psilocybin and psilocin are soluble in water, experiments wereconducted to determine if pH modulation could be beneficial in theextraction process (FIG. 32D).

High pH water was shown to extract and prevent degradation ofphosphorylated alkaloids, while low pH was shown to extract anddephosphorylate psilocybin but prevent laccase oxidation activity. Thisprocess was validated and can be used reliably to control thedephosphorylation process. On first look, it would appear that adrawback is that the use of high and low pH appears to be an “all ornone” process where there is no modulation of the dephosphorylationcascade.

However, combining the information gained from the water extraction pHstudy with the superior ability of methanol to extract these alkaloids,experiments were performed to see how this could be used to improve theprocess. An interesting result was revealed by varying themethanol/water ratio while fixing the pH with 5% acetic acid (˜pH 2.5,range 1-4) (FIG. 32E).

It was evident that the oxidation of psilocin during extraction was onlyweakly observed at the 0% methanol ratio, validating the previousexperimental data with low pH water extraction. Either protonation ofthe 4-hydroxy position on the psilocin molecule was inhibiting laccase'sability to catalyze the oxidation and free radical formation, or theenzyme was denatured and not active at this pH. Gradually, as themethanol concentration in the extraction solvent is increased, a higherproportion of the total alkaloid content is retained as thephosphorylated form, indicating that methanol is inhibiting ordrastically slowing phosphatase's ability to cleave the phosphate bond.Another possibility is that at a certain concentration, methanol is nolonger able to extract or solvate the phosphatase enzyme, leaving itbehind in the solid residue during extraction. This process can be usedto modulate the phosphorylated/dephosphorylated content of the extract.

Macroporous resin adsorption/desorption was chosen as a simple andefficient purification platform to concentrate the total alkaloidcontent since the concentration factor from extraction alone wasunderwhelming. Once the proper composition of alkaloids is determined(Table 8), a number of purification permutations can be utilized (Table9).

TABLE 8 Summary of extraction processes and conditions used EXTRACTIONGoal: Most preferred Less Preferred Phosphorylated Acidified AnhydrousHigh pH adjusted alkaloids left Methanol Water intact (Psilocybin,Anhydrous Methanol 80% Ethanol/Water Baeocystin, High pH Adjusted 80%Norbaeocystin, Ethanol/Water Aeruginascin) Dephosphorylated AcidifiedWater 50-70% Ethanol/Water Alkaloids Acidified 0-20% (Psilocin)methanol/water Specific Ratio Combine extracts of Psilocybin fromdifferent to Psilocin methods AFTER purification at specific ratioacidified 20-80% Methanol

TABLE 9 Summary of purification processes and condition PURIFICATIONGoal: Most preferred Less Preferred Highest Purity Repeated XAD4 SCX,SAX or other Resin Psilocybin column runs Antisolvent addition withacetone Liquid/liquid extraction Highest Purity XAD4 column XAD4 + SCXor Psilocin run + LXA817 antisolvent or liquid extraction PartialPurification of Single XAD4 psilocybin or psilocin run

Throughout the description, specific details have been set forth inorder to provide a more thorough understanding of the invention.However, the invention may be practised without these particulars. Inother instances, well known elements have not been shown or described indetail and repetitions of steps and features have been omitted to avoidunnecessarily obscuring the invention. Accordingly, the specificationand drawings are to be regarded in an illustrative, rather than arestrictive, sense.

All parameters, dimensions, materials, quantities and configurationsdescribed herein are examples only and may be changed depending on thespecific embodiment. Numbers and percentages are given to the nearestsignificant figure. For example, 10% includes the range between exactly9.5% and exactly 10.5%. Accordingly, the scope of the invention is to beconstrued in accordance with the substance defined by the claims. Theprocess may be scaled up using larger quantities and a modifiedapparatus.

The invention claimed is:
 1. A method for generating a phosphorylatedpsychoactive alkaloid extract comprising 0.1% to 99% by weight of apsychoactive alkaloid from a psychoactive organism, the methodcomprising: a. providing a biomass of the psychoactive organism; b.contacting the biomass with a solvent having a pH of greater than 7,wherein the psychoactive alkaloid comprises greater than 50% of aphosphorylated psychoactive alkaloid, wherein the solvent is a mixtureof an alcohol, water, and a base; c. removing the biomass from thesolvent; and d. evaporating the solvent after removing the biomass toyield the phosphorylated psychoactive alkaloid extract comprising 0.1%to 99% by weight of the psychoactive alkaloid.
 2. The method of claim 1,wherein, following (b), the biomass is contacted with a second solvent.3. The method of claim 1, wherein the alcohol comprises 60% to 99% ofthe mixture.
 4. The method of claim 3, wherein the alcohol is a C1-C4primary aliphatic alcohol.
 5. The method of claim 4, wherein the C1-C4primary aliphatic alcohol is ethanol or methanol.
 6. The method of claim1, wherein the psychoactive organism is Psilocybe cyanescens, Psilocybecubensis, Amanita muscaria, or any selection thereof.
 7. The method ofclaim 1, wherein the phosphorylated psychoactive alkaloid is psilocybin,baeocystin, norbaeocystin, aeruginascin, or any combination thereof. 8.The method of claim 1, wherein the solvent is present in an amount of 10milliliters (mL) to 100 mL.
 9. The method of claim 1, wherein thesolvent has a pH of 9 or more.
 10. The method of claim 1, wherein thesolvent has a pH of 10 or more.
 11. The method of claim 1, wherein thesolvent has a pH of 10.5 to 13.5.
 12. The method of claim 1, wherein thesolvent has a pH of 11 to
 12. 13. The method of claim 1, wherein thesolvent has a pH of
 13. 14. The method of claim 1, wherein thepsychoactive alkaloid is entirely the phosphorylated psychoactivealkaloid.
 15. The method of claim 1, wherein: the psychoactive organismcomprises phosphorylatable psychoactive alkaloid andnon-phosphorylatable psychoactive alkaloid; and the psychoactivealkaloid in the extract comprises the phosphorylatable psychoactivealkaloid and the non-phosphorylatable psychoactive alkaloid.
 16. Themethod of claim 15, wherein the phosphorylatable psychoactive alkaloidis 100% phosphorylated.
 17. The method of claim 1, wherein the pH of thesolvent is greater than 10.5 and a maximum concentration of thephosphorylated psychoactive alkaloid in the extract is limited by anamount of dephosphorylated psychoactive alkaloid in the biomass.
 18. Themethod of claim 1, comprising, between (c) and (d), adjusting the pH ofthe solvent to a pH ranging from 3.5 to 4.5.